Publications

Abstract

Eisenberg (2002) presents data from an experiment investigating three- and four-year-old children's comprehension of restrictive relative clauses (RC). From the results she argues, contrary to Hamburger & Crain (1982), that children do not have discourse knowledge of the felicity conditions of RCs before acquiring the syntax of relativization. This note evaluates this conclusion on the basis of the methodology used, and proposes that an account of syntactic development needs to be sensitive to the real-time processing requirements acquisition places on the learner.

Abstract

Gestures that spontaneously accompany speech convey information coordinated with the concurrent speech. There has been considerable theoretical disagreement about the process by which this informational coordination is achieved. Some theories predict that the information encoded in gesture is not influenced by how information is verbally expressed. However, others predict that gestures encode only what is encoded in speech. This paper investigates this issue by comparing informational coordination between speech and gesture across different languages. Narratives in Turkish, Japanese, and English were elicited using an animated cartoon as the stimulus. It was found that gestures used to express the same motion events were influenced simultaneously by (1) how features of motion events were expressed in each language, and (2) spatial information in the stimulus that was never verbalized. From this, it is concluded that gestures are generated from spatio-motoric processes that interact on-line with the speech production process. Through the interaction, spatio-motoric information to be expressed is packaged into chunks that are verbalizable within a processing unit for speech formulation. In addition, we propose a model of speech and gesture production as one of a class of frameworks that are compatible with the data.

Abstract

Nobel's legacy, or the metamorphosis of what is idealistic Ever since the first Nobel prize in literature was awarded to Prudhomme in 1901, the decisions of the Swedish Academy have been subject to criticism. What is surprising in the changing decision policy as well as in its criticism is the fact that Alfred Nobel's original intentions are hardly ever taken into account: the Nobel prize is a philanthropic prize, it is not meant to select and honour the most eminent literary work but the work with maximal benefit to human beings. What is even more surprising is the fact that no one seems to care that the donator's Last Will is regularly broken.

Abstract

In this article, we discuss the implications of the fact that adult second language learners (outside the classroom) universally develop a well-structured, efficient and simple form of language–the Basic Variety (BV). Three questions are asked as to (1) the structural properties of the BV, (2) the status of these properties and (3) why some structural properties of ‘fully fledged’ languages are more complex. First, we characterize the BV in four respects: its lexical repertoire, the principles according to which utterances are structured, and temporality and spatiality expressed. The organizational principles proposed are small in number, and interact. We analyse this interaction, describing how the BV is put to use in various complex verbal tasks, in order to establish both what its communicative potentialities are, and also those discourse contexts where the constraints come into conflict and where the variety breaks down. This latter phenomenon provides a partial answer to the third question,concerning the relative complexity of ‘fully fledged’ languages–they have devices to deal with such cases. As for the second question, it is argued firstly that the empirically established continuity of the adult acquisition process precludes any assignment of the BV to a mode of linguistic expression (e.g., ‘protolanguage’) distinct from that of ‘fully fledged’ languages and, moreover, that the organizational constraints of the BV belong to the core attributes of the human language capacity, whereas a number of complexifications not attested in the BV are less central properties of this capacity. Finally, it is shown that the notion of feature strength, as used in recent versions of Generative Grammar, allows a straightforward characterization of the BV as a special case of an I-language, in the sense of this theory. Under this perspective, the acquisition of an Ilanguage beyond the BV can essentially be described as a change in feature strength.

Abstract

During the last 25 years, second language acquisition (SLA) research hasmade considerable progress, but is still far from proving a solid basis for foreign language teaching, or from a general theory of SLA. In addition, its status within the linguistic disciplines is still very low. I argue this has not much to do with low empirical or theoretical standards in the field—in this regard, SLA research is fully competitive—but with a particular perspective on the acquisition process: SLA researches learners' utterances as deviations from a certain target, instead of genuine manifestations of underlying language capacity; it analyses them in terms of what they are not rather than what they are. For some purposes such a "target deviation perspective" makes sense, but it will not help SLA researchers to substantially and independently contribute to a deeper understanding of the structure and function of the human language faculty. Therefore, these findings will remain of limited interest to other scientists until SLA researchers consider learner varieties a normal, in fact typical, manifestation of this unique human capacity.

Abstract

To compare abstract structural and lexicalist accounts of syntactic processes in sentence formulation, we examined the effectiveness of nonidiomatic and idiomatic phrasal verbs in inducing structural generalizations. Three experiments made use of a syntactic priming paradigm in which participants recalled sentences they had read in rapid serial visual presentation. Prime and target sentences contained phrasal verbs with particles directly following the verb (pull off a sweatshirt) or following the direct object (pull a sweatshirt off). Idiomatic primes used verbs whose figurative meaning cannot be straightforwardly derived from the literal meaning of the main verb (e.g., pull off a robbery) and are commonly treated as stored lexical units. Particle placement in sentences was primed by both nonidiomatic and idiomatic verbs. Experiment 1 showed that the syntax of idiomatic and nonidiomatic phrasal verbs is amenable to priming, and Experiments 2 and 3 compared the priming patterns created by idiomatic and nonidiomatic primes. Despite differences in idiomaticity and structural flexibility, both types of phrasal verbs induced structural generalizations and differed little in their ability to do so. The findings are interpreted in terms of the role of abstract structural processes in language production.

Abstract

Source monitoring can be influenced by information that is external to the study context, such as beliefs and general knowledge (Johnson, Hashtroudi, & Lindsay, 1993). We investigated the extent to which metamnemonic judgments predict memory for items and sources when schematic information about the sources is or is not provided at encoding. Participants made judgments of learning (JOLs) to statements presented by two speakers and were informed of the occupation of each speaker either before or after the encoding session. Replicating earlier work, prior knowledge decreased participants' tendency to erroneously attribute statements to schematically consistent but episodically incorrect speakers. The origin of this effect can be understood by examining the relationship between JOLs and performance: JOLs were equally predictive of item and source memory in the absence of prior knowledge, but were exclusively predictive of source memory when participants knew of the relationship between speakers and statements during study. Background knowledge determines the information that people solicit in service of metamnemonic judgments, suggesting that these judgments reflect control processes during encoding that reduce schematic errors.

Abstract

Recognizing word boundaries in continuous speech requires detailed knowledge of the native language. In the first year of life, infants acquire considerable word segmentation abilities. Infants at this early stage in word segmentation rely to a large extent on the metrical pattern of their native language, at least in stress-based languages. In Dutch and English (both languages with a preferred trochaic stress pattern), segmentation of strong-weak words develops rapidly between 7 and 10 months of age. Nevertheless, trochaic languages contain not only strong-weak words but also words with a weak-strong stress pattern. In this article, we present electrophysiological evidence of the beginnings of weak-strong word segmentation in Dutch 10-month-olds. At this age, the ability to combine different cues for efficient word segmentation does not yet seem to be completely developed. We provide evidence that Dutch infants still largely rely on strong syllables, even for the segmentation of weak-strong words.

Abstract

The paper investigates the use of manner verbs (e.g. marcher 'to walk', courir 'to run') with so-called locative prepositions (e.g. dans 'in', sous 'under') in the descriptions of motion in French, as in Il a couru dans le bureau 'He ran in (to) the office', to explore the type of events such constructions express and the factors that influence their interpretation. Based on an extensive corpus survey, the study shows that, contrary to the general claim according to which such constructions express typically motion in some location, they are also frequently used to express change of location. The study discusses the interplay of various factors that contribute to the interpretation of these constructions, including semantic, aspectual and pragmatic factors.

Abstract

In various applications of forensic phonetics the question arises as to how far aural-perceptual speaker recognition performance is reliable. Therefore, it is necessary to examine the relationship between speaker recognition results and human perception/production abilities like musicality or speech sensitivity. In this study, performance in a speaker recognition experiment and a speech sensitivity test are correlated. The results show a moderately significant positive correlation between the two tasks. Generally, performance in the speaker recognition task was better than in the speech sensitivity test. Professionals in speech and singing yielded a more homogeneous correlation than non-experts. Training in speech as well as choir-singing seems to have a positive effect on performance in speaker recognition. It may be concluded, firstly, that in cases where the reliability of voice line-up results or the credibility of a testimony have to be considered, the speech sensitivity test could be a useful indicator. Secondly, the speech sensitivity test might be integrated into the canon of possible procedures for the accreditation of forensic phoneticians. Both tests may also be used in combination.

Abstract

Little is known about the genetic contribution to individual differences in neural networks subserving cognition function. In this functional magnetic resonance imaging (fMRI) twin study, we found a significant genetic influence on brain activation in neural networks supporting digit working memory tasks. Participants activating frontal-parietal networks responded faster than individuals relying more on language-related brain networks.There were genetic influences on brain activation in language-relevant brain circuits that were atypical for numerical working memory tasks as such. This suggests that differences in cognition might be related to brain activation patterns that differ qualitatively among individuals.

Abstract

Heterozygous mutations of the human FOXP2 gene cause a developmental disorder involving impaired learning and production of fluent spoken language. Previous investigations of its aetiology have focused on disturbed function of neural circuits involved in motor control. However, Foxp2 expression has been found in the cochlea and auditory brain centers and deficits in auditory processing could contribute to difficulties in speech learning and production. Here, we recorded auditory brainstem responses (ABR) to assess two heterozygous mouse models carrying distinct Foxp2 point mutations matching those found in humans with FOXP2-related speech/language impairment. Mice which carry a Foxp2-S321X nonsense mutation, yielding reduced dosage of Foxp2 protein, did not show systematic ABR differences from wildtype littermates. Given that speech/language disorders are observed in heterozygous humans with similar nonsense mutations (FOXP2-R328X), our findings suggest that auditory processing deficits up to the midbrain level are not causative for FOXP2-related language impairments. Interestingly, however, mice harboring a Foxp2-R552H missense mutation displayed systematic alterations in ABR waves with longer latencies (significant for waves I, III, IV) and smaller amplitudes (significant for waves I, IV) suggesting that either the synchrony of synaptic transmission in the cochlea and in auditory brainstem centers is affected, or fewer auditory nerve fibers and fewer neurons in auditory brainstem centers are activated compared to wildtypes. Therefore, the R552H mutation uncovers possible roles for Foxp2 in the development and/or function of the auditory system. Since ABR audiometry is easily accessible in humans, our data call for systematic testing of auditory functions in humans with FOXP2 mutations.

Abstract

Selected papers from the 18th International Conference on Historical Linguistics, Montreal, 6-11 August 2007

Abstract

Disruption of FOXP2, a gene encoding a forkhead-domain transcription factor, causes a severe developmental disorder of verbal communication, involving profound articulation deficits, accompanied by linguistic and grammatical impairments. Investigation of the neural basis of this disorder has been limited previously to neuroimaging of affected children and adults. The discovery of the gene responsible, FOXP2, offers a unique opportunity to explore the relevant neural mechanisms from a molecular perspective. In the present study, we have determined the detailed spatial and temporal expression pattern of FOXP2 mRNA in the developing brain of mouse and human. We find expression in several structures including the cortical plate, basal ganglia, thalamus, inferior olives and cerebellum. These data support a role for FOXP2 in the development of corticostriatal and olivocerebellar circuits involved in motor control. We find intriguing concordance between regions of early expression and later sites of pathology suggested by neuroimaging. Moreover, the homologous pattern of FOXP2/Foxp2 expression in human and mouse argues for a role for this gene in development of motor-related circuits throughout mammalian species. Overall, this study provides support for the hypothesis that impairments in sequencing of movement and procedural learning might be central to the FOXP2-related speech and language disorder.

Abstract

Investigations of left hand praxis in imitation and object use in patients with callosal disconnection have yielded divergent results, inducing a debate between two theoretical positions. Whereas Liepmann suggested that the left hemisphere is motor dominant, others maintain that both hemispheres have equal motor competences and propose that left hand apraxia in patients with callosal disconnection is secondary to left hemispheric specialization for language or other task modalities. The present study aims to gain further insight into the motor competence of the right hemisphere by investigating pantomime of object use in split-brain patients. Three patients with complete callosotomy and, as control groups, five patients with partial callosotomy and nine healthy subjects were examined for their ability to pantomime object use to visual object presentation and demonstrate object manipulation. In each condition, 11 objects were presented to the subjects who pantomimed or demonstrated the object use with either hand. In addition, six object pairs were presented to test bimanual coordination. Two independent raters evaluated the videotaped movement demonstrations. While object use demonstrations were perfect in all three groups, the split-brain patients displayed apraxic errors only with their left hands in the pantomime condition. The movement analysis of concept and execution errors included the examination of ipsilateral versus contralateral motor control. As the right hand/left hemisphere performances demonstrated retrieval of the correct movement concepts, concept errors by the left hand were taken as evidence for right hemisphere control. Several types of execution errors reflected a lack of distal motor control indicating the use of ipsilateral pathways. While one split-brain patient controlled his left hand predominantly by ipsilateral pathways in the pantomime condition, the error profile in the other two split-brain patients suggested that the right hemisphere controlled their left hands. In the object use condition, in all three split-brain patients fine-graded distal movements in the left hand indicated right hemispheric control. Our data show left hand apraxia in split-brain patients is not limited to verbal commands, but also occurs in pantomime to visual presentation of objects. As the demonstration with object in hand was unimpaired in either hand, both hemispheres must contain movement concepts for object use. However, the disconnected right hemisphere is impaired in retrieving the movement concept in response to visual object presentation, presumably because of a deficit in associating perceptual object representation with the movement concepts.

Abstract

Since some patients with right hemisphere damage or with spontaneous callosal disconnection neglect the left half of space, it has been suggested that the left cerebral hemisphere predominantly attends to the right half of space. However, clinical investigations of patients having undergone surgical callosal section have not shown neglect when the hemispheres are tested separately. These observations question the validity of theoretical models that propose a left hemispheric specialisation for attending to the right half of space. The present study aims to investigate neglect and the use of space by either hand in gestural demonstrations in three split-brain patients as compared to five patients with partial callosotomy and 11 healthy subjects. Subjects were asked to demonstrate with precise gestures and without speaking the content of animated scenes with two moving objects. The results show that in the absence of primary perceptual or representational neglect, split-brain patients neglect left personal space in right-handed gestural demonstrations. Since this neglect of left personal space cannot be explained by directional or spatial akinesia, it is suggested that it originates at the conceptual level, where the spatial coordinates for right-hand gestures are planned. The present findings are at odds with the position that the separate left hemisphere possesses adequate mechanisms for acting in both halves of space and neglect results from right hemisphere suppression of this potential. Rather, the results provide support for theoretical models that consider the left hemisphere as specialised for processing the right half of space during the execution of descriptive gestures.

Abstract

The present study investigates the hand choice in iconic gestures that accompany speech. In 10 right-handed subjects gestures were elicited by verbal narration and by silent gestural demonstrations of animations with two moving objects. In both conditions, the left-hand was used as often as the right-hand to display iconic gestures. The choice of the right- or left-hands was determined by semantic aspects of the message. The influence of hemispheric language lateralization on the hand choice in co-speech gestures appeared to be minor. Instead, speaking seemed to induce a sequential organization of the iconic gestures.

Abstract

We present a coding system combined with an annotation tool for the analysis of gestural behavior. The NEUROGES coding system consists of three modules that progress from gesture kinetics to gesture function. Grounded on empirical neuropsychological and psychological studies, the theoretical assumption behind NEUROGES is that its main kinetic and functional movement categories are differentially associated with specific cognitive, emotional, and interactive functions. ELAN is a free, multimodal annotation tool for digital audio and video media. It supports multileveled transcription and complies with such standards as XML and Unicode. ELAN allows gesture categories to be stored with associated vocabularies that are reusable by means of template files. The combination of the NEUROGES coding system and the annotation tool ELAN creates an effective tool for empirical research on gestural behavior.

Abstract

The purpose of this study was to relate a psycholinguistic processing model of picture naming to the dynamics of cortical activation during picture naming. The activation was recorded from eight Dutch subjects with a whole-head neuromagnetometer. The processing model, based on extensive naming latency studies, is a stage model. In preparing a picture's name, the speaker performs a chain of specific operations. They are, in this order, computing the visual percept, activating an appropriate lexical concept, selecting the target word from the mental lexicon, phonological encoding, phonetic encoding, and initiation of articulation. The time windows for each of these operations are reasonably well known and could be related to the peak activity of dipole sources in the individual magnetic response patterns. The analyses showed a clear progression over these time windows from early occipital activation, via parietal and temporal to frontal activation. The major specific findings were that (1) a region in the left posterior temporal lobe, agreeing with the location of Wernicke's area, showed prominent activation starting about 200 msec after picture onset and peaking at about 350 msec, (i.e., within the stage of phonological encoding), and (2) a consistent activation was found in the right parietal cortex, peaking at about 230 msec after picture onset, thus preceding and partly overlapping with the left temporal response. An interpretation in terms of the management of visual attention is proposed.

Abstract

This commentary discusses whether abstract metrical frames are stored. For stress-assigning languages (e.g., Dutch and English), which have a dominant stress pattern, metrical frames are stored only for words that deviate from the default stress pattern. The majority of the words in these languages are produced without retrieving any independent syllabic or metrical frame.

Abstract

The process of speaking is traditionally regarded as a mapping of thoughts (intentions, feelings, etc.) onto language. One requirement that this mapping has to meet is that the units of information to be expressed be strictly ordered. The channel of speech largely prohibits the simultaneous expression of multiple propositions: the speaker has a linearization problem - that is, a linear order has to be determined over any knowledge structure to be formulated. This may be relatively simple if the informational structure has itself an intrinsic linear arrangement, as often occurs with event structures, but it requires special procedures if the structure is more complex, as is often the case in two- or three-dimensional spatial patterns. How, for instance, does a speaker proceed in describing his home, or the layout of his town? Two powerful constraints on linearization derive, on the one hand, from 'mutual knowledge' and, on the other, from working memory limitations. Mutual knowledge may play a role in that the listener can be expected to derive different implicatures from different orderings (compare 'she married and became pregnant' with 'she became pregnant and married'). Mutual knowledge determinants of linearization are essentially pragmatic and cultural, and dependent on the content of discourse. Working memory limitations affect linearization in that a speaker's linearization strategy will minimize memory load during the process of formulating. A multidimensional structure is broken up in such a way that the number of 'return addresses' to be kept in memory will be minimized. This is attained by maximizing the connectivity of the discourse, and by backtracking to stored addresses in a first-in-last-out fashion. These memory determinants of linearization are presumably biological, and independent of the domain of discourse. An important question is whether the linearization requirement is enforced by the oral modality of speech or whether it is a deeper modality-independent property of language use.

Abstract

The core issue in the 19-century sources of psycholinguistics was the question, "Where does language come from?'' This genetic perspective unified the study of the ontogenesis, the phylogenesis, the microgenesis, and to some extent the neurogenesis of language. This paper makes the point that this original perspective is still a valid and attractive one. It is exemplified by a discussion of the genesis of spoken words.

Abstract

This is a translation of Levinson and Brown (1994).

Abstract

Most approaches to spatial language have assumed that the simplest spatial notions are (after Piaget) topological and universal (containment, contiguity, proximity, support, represented as semantic primitives suchas IN, ON, UNDER, etc.). These concepts would be coded directly in language, above all in small closed classes suchas adpositions—thus providing a striking example of semantic categories as language-specific projections of universal conceptual notions. This idea, if correct, should have as a consequence that the semantic categories instantiated in spatial adpositions should be essentially uniform crosslinguistically. This article attempts to verify this possibility by comparing the semantics of spatial adpositions in nine unrelated languages, with the help of a standard elicitation procedure, thus producing a preliminary semantic typology of spatial adpositional systems. The differences between the languages turn out to be so significant as to be incompatible withstronger versions of the UNIVERSAL CONCEPTUAL CATEGORIES hypothesis. Rather, the language-specific spatial adposition meanings seem to emerge as compact subsets of an underlying semantic space, withcertain areas being statistical ATTRACTORS or FOCI. Moreover, a comparison of systems withdifferent degrees of complexity suggests the possibility of positing implicational hierarchies for spatial adpositions. But such hierarchies need to be treated as successive divisions of semantic space, as in recent treatments of basic color terms. This type of analysis appears to be a promising approachfor future work in semantic typology.

Abstract

This article explores the relation between language and cognition by examining the case of "absolute" (cardinal direction) spatial description in the Australian aboriginal language Guugu Yimithirr. This kind of spatial description is incongruent with the "relative" (e.g., left/right/front/back) spatial description familiar in European languages. Building on Haviland's 1993 analysis of Guugu Yimithirr directionals in speech and gesture, a series of informal experiments were developed. It is shown that Guugu Yimithirr speakers predominantly code for nonverbal memory in "absolute" concepts congruent with their language, while a comparative sample of Dutch speakers do so in "relative" concepts. Much anecdotal evidence also supports this. The conclusion is that Whorfian effects may in fact be demonstrable in the spatial domain.

Abstract

This short report draws attention to an interesting kind of configuration in the lexicon that seems to have escaped theoretical or systematic descriptive attention. These configurations, which we dub SEMPLATES, consist of an abstract structure or template, which is recurrently instantiated in a number of lexical sets, typically of different form classes. A number of examples from different language families are adduced, and generalizations made about the nature of semplates, which are contrasted to other, perhaps similar, phenomena

Abstract

Focuses on the pre-observations on the modeling of dialogue. Assumptions that underlie speech act models of dialogue; Identifiability of utterance units corresponding to unit acts; Capacity of the models to model the actual properties of natural dialogue.

Abstract

Philosophers, psychologists, and linguists have argued that spatial conception is pivotal to cognition in general, providing a general, egocentric, and universal framework for cognition as well as metaphors for conceptualizing many other domains. But in an aboriginal community in Northern Queensland, a system of cardinal directions informs not only language, but also memory for arbitrary spatial arrays and directions. This work suggests that fundamental cognitive parameters, like the system of coding spatial locations, can vary cross-culturally, in line with the language spoken by a community. This opens up the prospect of a fruitful dialogue between anthropology and the cognitive sciences on the complex interaction between cultural and universal factors in the constitution of mind.

Abstract

We propose that the choice between the auxiliaries hebben 'have' and zijn 'be' in Dutch is determined by a particular semantic feature of verbs. In particular we propose a feature of meaning [IEPS] for 'inferable eventual position or state' that characterizes whether the action denoted by the verb allows us to determine the eventual position or state of the verb's highest argument. It is argued that only verbs which exhibit the feature [+IEPS] or which obtain the feature compositionally in the syntax select zijn as their auxiliary. Our analysis is then compared to a number of other analyses of auxiliary selection in Dutch.

Abstract

Most neuroimaging studies are performed using one imaging method only, either functional magnetic resonance imaging (fMRI), electroencephalography (EEG), or magnetoencephalography (MEG). Information on both location and timing has been sought by recording fMRI and EEG, simultaneously, or MEG and fMRI in separate sessions. Such approaches assume similar active areas whether detected via hemodynamic or electrophysiological signatures. Direct comparisons, after independent analysis of data from each imaging modality, have been conducted primarily on low-level sensory processing. Here, we report MEG (timing and location) and fMRI (location) results in 11 subjects when they named pictures that depicted an action or an object. The experimental design was exactly the same for the two imaging modalities. The MEG data were analyzed with two standard approaches: a set of equivalent current dipoles and a distributed minimum norm estimate. The fMRI blood-oxygenlevel dependent (BOLD) data were subjected to the usual random-effect contrast analysis. At the group level, MEG and fMRI data showed fairly good convergence, with both overall activation patterns and task effects localizing to comparable cortical regions. There were some systematic discrepancies, however, and the correspondence was less compelling in the individual subjects. The present analysis should be helpful in reconciling results of fMRI and MEG studies on high-level cognitive functions

Abstract

Recent research suggests that 12-month-old infants in German cultural settings have the motive of sharing their attention to and interest in various events with a social interlocutor. To do so, these preverbal infants predominantly use the pointing gesture (in this case the extended arm with or without extended index finger) as a means to direct another person’s attention. This task systematically investigates different types of motives underlying infants’ pointing. The occurrence of a protodeclarative (as opposed to protoimperative) motive is of particular interest because it requires an understanding of the recipient’s psychological states, such as attention and interest, that can be directed and accessed.

Abstract

One of the defining features of human language is displacement, the ability to make reference to absent entities. Here we show that prelinguistic, 12-month-old infants already can use a nonverbal pointing gesture to make reference to absent entities. We also show that chimpanzees—who can point for things they want humans to give them—do not point to refer to absent entities in the same way. These results demonstrate that the ability to communicate about absent but mutually known entities depends not on language, but rather on deeper social-cognitive skills that make acts of linguistic reference possible in the first place. These nonlinguistic skills for displaced reference emerged apparently only after humans' divergence from great apes some 6 million years ago.

Abstract

Mutations of the renal-specific chloride channel (CLCN5) gene, which is located on chromosome Xp11.22, are associated with hypercalciuric nephrolithiasis (kidney stones) in the Northern European and Japanese populations. CLCN5 encodes a 746 amino acid channel (CLC-5) that has approximately 12 transmembrane domains, and heterologous expression of wild-type CLC-5 in Xenopus oocytes has yielded outwardly rectifying chloride currents that were markedly reduced or abolished by these mutations. In order to assess further the structural and functional relationships of this recently cloned chloride channel, additional CLCN5 mutations have been identified in five unrelated families with this disorder. Three of these mutations were missense (G57V, G512R and E527D), one was a nonsense (R648Stop) and one was an insertion (30:H insertion). In addition, two of the mutations (30:H insertion and E527D) were demonstrated to be de novo, and the G57V and E527D mutations were identified in families of Afro-American and Indian origin, respectively. The G57V and 30:H insertion mutations represent the first CLCN5 mutations to be identified in the N-terminus region, and the R648Stop mutation, which has been observed previously in an unrelated family, suggests that this codon may be particularly prone to mutations. Heterologous expression of the mutations resulted in a marked reduction or abolition of the chloride currents, thereby establishing their functional importance. These results help to elucidate further the structure-function relationships of this renal chloride channel.