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Zoha Kibar - One of the best experts on this subject based on the ideXlab platform.
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a 1 5 mb physical map of the Hidrotic Ectodermal Dysplasia clouston syndrome gene region on human chromosome 13q11
Genomics, 2000Co-Authors: Jérôme Lamartine, Guy A Rouleau, Zoha Kibar, P. Soularue, Amandine Pitaval, Isabelle Lanneluc, Gilles Lemaitre, Gilles WaksmanAbstract:The HED (Hidrotic Ectodermal Dysplasia) or Clouston syndrome gene (named ED2) has been mapped to the pericentromeric region of chromosome 13 (13q11) to a 2.4-cM interval flanked by markers D13S1828 and D13S1830. We have developed a BAC/PAC-based contig map of this region. This contig, comprising 23 clones and spanning 1.5 Mb, was established by mapping of 27 BAC/PAC end-derived STSs, 11 known polymorphic markers, 2 previously mapped genes, and 14 ESTs. The genomic clone overlaps were confirmed by restriction fragment fingerprint analysis. This contig provides the basis for genomic sequencing and gene identification in the ED2 critical region. Of the 14 ESTs mapped to the contig, 6 show homology to human genes and 8 appear to be novel. Expression patterns of the genes/ESTs were tested by Northern blot and RT-PCR. Full characterization of some of these genes, as well as the novel ESTs, will be useful in assessing their involvement in the HED/Clouston syndrome.
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clouston Hidrotic Ectodermal Dysplasia hed genetic homogeneity presence of a founder effect in the french canadian population and fine genetic mapping
European Journal of Human Genetics, 2000Co-Authors: Zoha Kibar, Susan J. Hayflick, Alain Hovnanian, Jonathan Zonana, Mariepierre Dube, Julie Powell, Catherine Mccuaig, Uppala RadhakrishnaAbstract:HED is an autosomal dominant skin disorder that is particularly common in the French Canadian population of south-west Quebec. We previously mapped the HED gene to the pericentromeric region of chromosome 13q using linkage analysis in eight French Canadian families. In this study, we extend our genetic analysis to include a multiethnic group of 29 families with 10 polymorphic markers spanning 5.1 cM in the candidate region. Two-point linkage analysis strongly suggests absence of genetic heterogeneity in HED in four families of French, Spanish, African and Malaysian origins. Multipoint linkage analysis in all 29 families generated a peak lod score of 53.5 at D13S1835 with a 1 lod unit support interval spanning 1.8 cM. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. We next show evidence for a strong founder effect in families of French Canadian origin thereby representing the first example of a founder disease in the south-west part of the province of Quebec. Significant association was found between HED in these families and all markers analysed (Fisher's exact test, P < 0.001). Complete allelic association was detected at D13S1828, D13S1827, D13S1835, D13S141 and D13S175 (P(excess) = 1) spanning 1.3 cM. A major haplotype including all 10 associated alleles was present on 65% of affected chromosomes. This haplotype most likely represents the founder haplotype that introduced the HED mutation into the French Canadian population. Luria-Delbruck equations and multipoint likelihood linkage disequilibrium analysis positioned the gene at the D13S1828 locus (likely range estimate: 1.75 cM) and 0.58 cM telomeric to this marker (support interval: 3.27 cM) respectively.
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Clouston Hidrotic Ectodermal Dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping
European Journal of Human Genetics, 2000Co-Authors: Zoha Kibar, Susan J. Hayflick, Alain Hovnanian, Jonathan Zonana, Uppala Radhakrishna, Stylianos E. Antonarakis, Mariepierre Dube, Julie Powell, Catherine Mccuaig, Antranik BenohanianAbstract:HED is an autosomal dominant skin disorder that is particularly common in the French Canadian population of south-west Quebec. We previously mapped the HED gene to the pericentromeric region of chromosome 13q using linkage analysis in eight French Canadian families. In this study, we extend our genetic analysis to include a multiethnic group of 29 families with 10 polymorphic markers spanning 5.1 cM in the candidate region. Two-point linkage analysis strongly suggests absence of genetic heterogeneity in HED in four families of French, Spanish, African and Malaysian origins. Multipoint linkage analysis in all 29 families generated a peak lod score of 53.5 at D13S1835 with a 1 lod unit support interval spanning 1.8 cM. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. We next show evidence for a strong founder effect in families of French Canadian origin thereby representing the first example of a founder disease in the south-west part of the province of Quebec. Significant association was found between HED in these families and all markers analysed (Fisher's exact test, P
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Refined localization of the gene for Clouston syndrome (Hidrotic Ectodermal Dysplasia) in a large French family
The British journal of dermatology, 2000Co-Authors: Jérôme Lamartine, Guy A Rouleau, Zoha Kibar, D. Laoudj, C. Blanchet-bardon, P. Soularue, V. Ridoux, L. Dubertret, Gilles WaksmanAbstract:Hidrotic Ectodermal Dysplasia (HED) or Clouston syndrome is a rare autosomal dominant disorder characterized by nail dystrophy, alopecia and palmoplantar hyperkeratosis, which maps to chromosome 13q11-q12.1. We confirmed linkage of HED to this region in a large French family. To define the critical region for HED, detailed haplotypes were constructed with new pericentromeric polymorphic markers. A recombination event in the family indicates that the HED locus maps centromeric to D13S1832. Our French family does not share a common haplotype with other pedigrees previously published (particularly French-Canadian), indicating that the mutations in these families are likely to be of different origin.
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a radiation hybrid map of 48 loci including the clouston Hidrotic Ectodermal Dysplasia locus in the pericentromeric region of chromosome 13q
Genomics, 1999Co-Authors: Ronald G Lafreniere, Mario Chevrette, Jia-chi Wang, Zoha Kibar, Aravinda Chakravarti, Vazken Der M KaloustianAbstract:Abstract To facilitate the identification of the gene responsible for Clouston Hidrotic Ectodermal Dysplasia (HED), we used a chromosome 13-specific radiation hybrid panel to map 54 loci in the HED candidate region. The marker retention data were analyzed using RHMAP version 3. The 54 markers have an average retention frequency of 31.6% with decreasing retention as a function of distance from the centromere. Two-point analysis identified three linkage groups with a threshold lod score of 4.00; one linkage group consisted of 49 loci including the centromeric marker D13Z1 and the telomeric flanking marker for the HED candidate region D13S143. Assuming a centromeric retention model, multipoint maximum likelihood analysis of these 49 loci except D13Z1 provided a 1000:1 framework map ordering 29 loci with 21 unique map positions and ∼2000 times more likely than the next order. Loci that could not be ordered with this level of support were positioned within a range of adjacent intervals. This map spans 347 cR 9000 , has an average resolution of 17.3 cR 9000 , and includes 3 genes (TUBA2, GJβ2, and FGF-9), 18 ESTs, 19 polymorphic loci, and 8 single-copy DNA segments. Comparison of our RH map to a YAC contig showed an inconsistency in order involving a reversed interval of 6 loci. Fiber-FISH and FISH on interphase nuclei analyses with PACs isolated from this region supported our order. We also describe the isolation of 8 new chromosome 13q polymorphic (CA) n markers that have an average PIC value of 0.67. These data and mapping reagents will facilitate the isolation of disease genes from this region.
Gilles Waksman - One of the best experts on this subject based on the ideXlab platform.
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Connexin30 mutations responsible for Hidrotic Ectodermal Dysplasia cause abnormal hemichannel activity
Human molecular genetics, 2004Co-Authors: Guilherme Munhoz Essenfelder, Jérôme Lamartine, Roberto Bruzzone, Anne Charollais, Claudine Blanchet-bardon, Michael T. Barbe, Paolo Meda, Gilles WaksmanAbstract:Clouston syndrome or Hidrotic Ectodermal Dysplasia (HED) is a rare dominant genodermatosis characterized by palmoplantar hyperkeratosis, generalized alopecia and nail defects. The disease is caused by mutations in the human GJB6 gene which encodes the gap junction protein connexin30 (Cx30). To gain insight into the molecular mechanisms underlying HED, we have analyzed the consequences of two of these mutations (G11R Cx30 and A88V Cx30) on the functional properties of the connexons they form. Here, we show that the distribution of Cx30 is similar in affected palmoplantar skin and in normal epidermis. We further demonstrate that the presence of the wild-type protein (wt Cx30) improves the trafficking of mutated Cx30 to the plasma membrane where both G11R and A88V Cx30 co-localize with wt Cx30 and form functional intercellular channels. The electrophysiological properties of channels made of G11R and A88V Cx30 differ slightly from those of wt Cx30 but allow for dye transfer between transfected HeLa cells. Finally, we document a gain of function of G11R and A88V Cx30, which form functional hemichannels at the cell surface and, when expressed in HeLa cells, generate a leakage of ATP into the extracellular medium. Such increased ATP levels might act as a paracrine messenger that, by altering the epidermal factors which control the proliferation and differentiation of keratinocytes, may play an important role in the pathophysiological processes leading to the HED phenotype.
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a 1 5 mb physical map of the Hidrotic Ectodermal Dysplasia clouston syndrome gene region on human chromosome 13q11
Genomics, 2000Co-Authors: Jérôme Lamartine, Guy A Rouleau, Zoha Kibar, P. Soularue, Amandine Pitaval, Isabelle Lanneluc, Gilles Lemaitre, Gilles WaksmanAbstract:The HED (Hidrotic Ectodermal Dysplasia) or Clouston syndrome gene (named ED2) has been mapped to the pericentromeric region of chromosome 13 (13q11) to a 2.4-cM interval flanked by markers D13S1828 and D13S1830. We have developed a BAC/PAC-based contig map of this region. This contig, comprising 23 clones and spanning 1.5 Mb, was established by mapping of 27 BAC/PAC end-derived STSs, 11 known polymorphic markers, 2 previously mapped genes, and 14 ESTs. The genomic clone overlaps were confirmed by restriction fragment fingerprint analysis. This contig provides the basis for genomic sequencing and gene identification in the ED2 critical region. Of the 14 ESTs mapped to the contig, 6 show homology to human genes and 8 appear to be novel. Expression patterns of the genes/ESTs were tested by Northern blot and RT-PCR. Full characterization of some of these genes, as well as the novel ESTs, will be useful in assessing their involvement in the HED/Clouston syndrome.
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Refined localization of the gene for Clouston syndrome (Hidrotic Ectodermal Dysplasia) in a large French family
The British journal of dermatology, 2000Co-Authors: Jérôme Lamartine, Guy A Rouleau, Zoha Kibar, D. Laoudj, C. Blanchet-bardon, P. Soularue, V. Ridoux, L. Dubertret, Gilles WaksmanAbstract:Hidrotic Ectodermal Dysplasia (HED) or Clouston syndrome is a rare autosomal dominant disorder characterized by nail dystrophy, alopecia and palmoplantar hyperkeratosis, which maps to chromosome 13q11-q12.1. We confirmed linkage of HED to this region in a large French family. To define the critical region for HED, detailed haplotypes were constructed with new pericentromeric polymorphic markers. A recombination event in the family indicates that the HED locus maps centromeric to D13S1832. Our French family does not share a common haplotype with other pedigrees previously published (particularly French-Canadian), indicating that the mutations in these families are likely to be of different origin.
Jonathan Zonana - One of the best experts on this subject based on the ideXlab platform.
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American Journal of Medical Genetics 47:550-555 (1993) Congenital Contractures, Ectodermal Dysplasia, Cleft Lip/Palate, and Developmental Impairment: A Distinct Syndrome
2016Co-Authors: Roger L. Ladda, Jonathan Zonana, Jeanette C. Ramer, Maria J. Mascari, Peter K. RoganAbstract:Brothers were affected with severe congenital contractures, multiple cutaneous manifesta-tions of Ectodermal Dysplasia, cleft liplpalate, and psychomotor and growth impairment. High resolution prometaphase chromosomes were normal. Molecular studies of DNA markers, closely flanking the X-linked hypo-Hidrotic Ectodermal Dysplasia locus, did not show evidence of a submicroscopic deletion from the Xq12-ql3 region. The parents and a normal sister exhibited none of these findings. This constellation of anomalies appears to represent a unique AR o r XLR syndrome. 0 1993 Wiley-Liss, Inc. KEY WORDS: congenital contractures, ecto-dermal Dysplasia, cleft lip
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clouston Hidrotic Ectodermal Dysplasia hed genetic homogeneity presence of a founder effect in the french canadian population and fine genetic mapping
European Journal of Human Genetics, 2000Co-Authors: Zoha Kibar, Susan J. Hayflick, Alain Hovnanian, Jonathan Zonana, Mariepierre Dube, Julie Powell, Catherine Mccuaig, Uppala RadhakrishnaAbstract:HED is an autosomal dominant skin disorder that is particularly common in the French Canadian population of south-west Quebec. We previously mapped the HED gene to the pericentromeric region of chromosome 13q using linkage analysis in eight French Canadian families. In this study, we extend our genetic analysis to include a multiethnic group of 29 families with 10 polymorphic markers spanning 5.1 cM in the candidate region. Two-point linkage analysis strongly suggests absence of genetic heterogeneity in HED in four families of French, Spanish, African and Malaysian origins. Multipoint linkage analysis in all 29 families generated a peak lod score of 53.5 at D13S1835 with a 1 lod unit support interval spanning 1.8 cM. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. We next show evidence for a strong founder effect in families of French Canadian origin thereby representing the first example of a founder disease in the south-west part of the province of Quebec. Significant association was found between HED in these families and all markers analysed (Fisher's exact test, P < 0.001). Complete allelic association was detected at D13S1828, D13S1827, D13S1835, D13S141 and D13S175 (P(excess) = 1) spanning 1.3 cM. A major haplotype including all 10 associated alleles was present on 65% of affected chromosomes. This haplotype most likely represents the founder haplotype that introduced the HED mutation into the French Canadian population. Luria-Delbruck equations and multipoint likelihood linkage disequilibrium analysis positioned the gene at the D13S1828 locus (likely range estimate: 1.75 cM) and 0.58 cM telomeric to this marker (support interval: 3.27 cM) respectively.
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Clouston Hidrotic Ectodermal Dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping
European Journal of Human Genetics, 2000Co-Authors: Zoha Kibar, Susan J. Hayflick, Alain Hovnanian, Jonathan Zonana, Uppala Radhakrishna, Stylianos E. Antonarakis, Mariepierre Dube, Julie Powell, Catherine Mccuaig, Antranik BenohanianAbstract:HED is an autosomal dominant skin disorder that is particularly common in the French Canadian population of south-west Quebec. We previously mapped the HED gene to the pericentromeric region of chromosome 13q using linkage analysis in eight French Canadian families. In this study, we extend our genetic analysis to include a multiethnic group of 29 families with 10 polymorphic markers spanning 5.1 cM in the candidate region. Two-point linkage analysis strongly suggests absence of genetic heterogeneity in HED in four families of French, Spanish, African and Malaysian origins. Multipoint linkage analysis in all 29 families generated a peak lod score of 53.5 at D13S1835 with a 1 lod unit support interval spanning 1.8 cM. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. We next show evidence for a strong founder effect in families of French Canadian origin thereby representing the first example of a founder disease in the south-west part of the province of Quebec. Significant association was found between HED in these families and all markers analysed (Fisher's exact test, P
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Confirmation of linkage of Clouston syndrome (Hidrotic Ectodermal Dysplasia) to 13q11-q12.1 with evidence for multiple independent mutations.
The Journal of investigative dermatology, 1998Co-Authors: Todd D. Taylor, Susan J. Hayflick, Wendy Mckinnon, Alan E. Guttmacher, Alain Hovnanian, M. Litt, Jonathan ZonanaAbstract:Clouston syndrome (Hidrotic Ectodermal Dysplasia) is an autosomal dominant disorder characterized by the triad of nail dystrophy, alopecia, and palmoplantar hyperkeratosis. Recently, linkage of a Clouston syndrome locus to chromosome 13q11-q12.1 was reported in eight families of French-Canadian descent. We have confirmed linkage to this region in four additional families: two of French-Canadian descent, one of Scottish–Irish descent, and one French family. Multipoint linkage analysis gave a lod score of 5.09 at marker D13S175. The two families of French-Canadian descent share haplotypes with those reported by Kibar et al. (1996), indicating a common founder. The French and Scottish–Irish families do not demonstrate the common haplotype, indicating that the mutations in these populations are most likely of different origin.
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clouston syndrome Hidrotic Ectodermal Dysplasia is not linked to keratin gene clusters on chromosomes 12 and 17
Journal of Investigative Dermatology, 1996Co-Authors: Susan J. Hayflick, Todd D. Taylor, Wendy Mckinnon, Alan E. Guttmacher, M. Litt, Jonathan ZonanaAbstract:Clouston syndrome is an Hidrotic form of Ectodermal Dysplasia, inherited as an autosomal dominant trait with high penetrance. The main features of the disorder are alopecia, severe dystrophy of the nails, and palmoplantar hyperkeratosis. A molecular abnormality of keratin has long been hypothesized to be the basic defect in this disorder. We have performed linkage analyses between the disorder and markers close to the keratin gene clusters on chromosomes 12 and 17 and have excluded linkage to these candidate regions in three apparently unrelated families. In addition, linkage has been excluded to four other candidate regions including 1q21, 17q23-qter, 18q21, and 20q12. These data indicate that Cloustoun syndrome is not due to a defect in keratin or in a subset of keratin-associated proteins.
Guy A Rouleau - One of the best experts on this subject based on the ideXlab platform.
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Alopecia Areata Universalis in an Infant
Journal of Cutaneous Medicine and Surgery, 2001Co-Authors: Jo Anne Larow, Guy A Rouleau, Judith Mysliborski, I. Paul Rappaport, J. Andrew CarlsonAbstract:Background: Alopecia areata (AA) is common during childhood and rarely reported in infants. The four reported cases of AA in infants all exhibited circumscribed patches of alopecia that appeared at birth or shortly thereafter. Objective: We report a case of alopecia areata universalis that developed after birth along with fingernail changes of shortening (onychomadesis) and onycholysis. Scalp biopsy at 2 years of age revealed rare, intermediate, terminal follicles in catagen associated with sparse peribulbar lymphocytic infiltrates. Results: This constellation of clinicopathologic features was interpreted as AA. We discuss the differential diagnosis of generalized alopecia in healthy infants, in particular, Clouston's syndrome, a hair-nail (Hidrotic) Ectodermal Dysplasia found in this region. Genetic testing for linked polymorphisms to the Clouston gene locus were negative in this child and his parents. Conclusions: Alopecia areata should be included in the differential diagnosis of generalized alopecia presenting at or shortly after birth. For purposes of genetic counseling and prognosis, it is crucial that a correct diagnosis be made.
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a 1 5 mb physical map of the Hidrotic Ectodermal Dysplasia clouston syndrome gene region on human chromosome 13q11
Genomics, 2000Co-Authors: Jérôme Lamartine, Guy A Rouleau, Zoha Kibar, P. Soularue, Amandine Pitaval, Isabelle Lanneluc, Gilles Lemaitre, Gilles WaksmanAbstract:The HED (Hidrotic Ectodermal Dysplasia) or Clouston syndrome gene (named ED2) has been mapped to the pericentromeric region of chromosome 13 (13q11) to a 2.4-cM interval flanked by markers D13S1828 and D13S1830. We have developed a BAC/PAC-based contig map of this region. This contig, comprising 23 clones and spanning 1.5 Mb, was established by mapping of 27 BAC/PAC end-derived STSs, 11 known polymorphic markers, 2 previously mapped genes, and 14 ESTs. The genomic clone overlaps were confirmed by restriction fragment fingerprint analysis. This contig provides the basis for genomic sequencing and gene identification in the ED2 critical region. Of the 14 ESTs mapped to the contig, 6 show homology to human genes and 8 appear to be novel. Expression patterns of the genes/ESTs were tested by Northern blot and RT-PCR. Full characterization of some of these genes, as well as the novel ESTs, will be useful in assessing their involvement in the HED/Clouston syndrome.
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Refined localization of the gene for Clouston syndrome (Hidrotic Ectodermal Dysplasia) in a large French family
The British journal of dermatology, 2000Co-Authors: Jérôme Lamartine, Guy A Rouleau, Zoha Kibar, D. Laoudj, C. Blanchet-bardon, P. Soularue, V. Ridoux, L. Dubertret, Gilles WaksmanAbstract:Hidrotic Ectodermal Dysplasia (HED) or Clouston syndrome is a rare autosomal dominant disorder characterized by nail dystrophy, alopecia and palmoplantar hyperkeratosis, which maps to chromosome 13q11-q12.1. We confirmed linkage of HED to this region in a large French family. To define the critical region for HED, detailed haplotypes were constructed with new pericentromeric polymorphic markers. A recombination event in the family indicates that the HED locus maps centromeric to D13S1832. Our French family does not share a common haplotype with other pedigrees previously published (particularly French-Canadian), indicating that the mutations in these families are likely to be of different origin.
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the gene responsible for clouston Hidrotic Ectodermal Dysplasia maps to the pericentromeric region of chromosome 13q
Human Molecular Genetics, 1996Co-Authors: Zoha Kibar, Valerie Hani, Clarke F Fraser, Vazken Der M Kaloustian, Bernard Brais, Guy A RouleauAbstract:: Hidrotic Ectodermal Dysplasia (HED), Clouston type, is an autosomal dominant skin disorder which is most common in the French-Canadian population and is characterized by hair defects, nail dystrophy and palmoplantar hyperkeratosis. Biophysical and biochemical studies conducted in HED suggested a molecular abnormality of keratins. We tested eight French-Canadian families segregating HED for linkage to microsatellite markers flanking the known keratin genes and were able to exclude linkage to these loci. Therefore, a genome-wide search for the HED gene was initiated. The first lod score above 3.00 was obtained with the marker D13S175 located in the pericentromeric region of chromosome 13q (Zmax = 8.12 at zero recombination). The cumulative lod scores were above 3.00 for six other markers in the region. A multipoint linkage analysis using the markers D13S175, D13S141 and D13S143 gave a maximum lod score of 11.12 at D13S141 with the one-lod-unit support interval spanning a 12.7 cM region which includes D13S175 and D13S141. Haplotype analysis allowed us to establish D13S143 as the telomeric flanking marker for the HED candidate region.
David H. Weaver - One of the best experts on this subject based on the ideXlab platform.
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Clouston syndrome: an ultrastructural study.
Clinical Genetics, 2008Co-Authors: Victor H. Escobar, Lawrence I. Goldblatt, David Bixler, David H. WeaverAbstract:A previously undescribed French-Canadian family affected with Clouston Syndrome (Hypo-Hidrotic Ectodermal Dysplasia) is described. Ultrastructural study of the hair shows disorganization of the hair fibrils with loss of the cuticular cortex. The SEM findings are consistent with the model, suggesting a biochemical defect in the keratin of the integumentary system.