The gene for autosomal dominant hidrotic ectodermal dysplasia (Clouston syndrome) in a large Indian family maps to the 13q11-q12.1 pericentromeric region

Abstract

Hidrotic ectodermal dysplasia (HED), Clouston syndrome (MIM No. 129500), is an autosomal dominant disorder affecting the skin and its derivatives. It is characterized by alopecia, dysplastic nails in hands and feet, and hyperkeratosis of the palms and soles. We have studied a large Indian pedigree (UR005), from Gujarat region, consisting of a total 127 individuals including 41 affected (12 males and 29 females). The phenotype in this family ranged from atrichosis to hypotrichosis, sparsity or absence of eyebrows, and thickening of palms and soles. In order to map the disease locus by linkage analysis, DNA polymorphisms were used in DNAs from 23 affected and 8 normal individuals. While genotyping was in progress, Kibar et al. [1996] reported mapping of the locus of a similar disease in French-Canadian families to 13q around marker D13S141. We then utilized markers on 13q to genotype the members of the Indian family. Linkage with 13q11-12.1 markers was confirmed with a maximum lod score of 3.27 (theta=0.00) with locus D13S1316. Multipoint linkage analysis yielded a lod score of 5.04 at theta=0.00 with D13S1316; haplotype analysis indicated that the gene for the Clouston syndrome in this family is localized proximal to D13S292. These data suggest that the gene for the Clouston syndrome in this Indian pedigree is probably the same as that described in the French Canadian families. The combination of data from all available families linked to 13q11-12.1 will make it possible to narrow the critical region and facilitate the positional cloning of the elusive gene.

Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping

“…5,6,9 Our results extend this finding to include families of African, Spanish, French and Malaysian origins. The African family was diagnosed as having a new form of ectodermal dysplasia different from HED, based mainly on the associated abnormal cardiac findings and absence of palmoplantar keratoderma in the affected members.…”

“…Linkage in the Indian and Scottish-Irish families to this region was previously demonstrated; 5,6 this study extends the genotyping analysis of these families with seven new markers. Table 1 shows the maximum lod scores obtained with each marker.…”

“…The Indian, Scottish-Irish, and South African families have been previously described. 5,12,13 The French family was collected by AH in the UK; two branches of this family have been reported by Giraud et al 14 and Taylor et al 6 The Malaysian family was described by Stevens et al 15 The Spanish family was collected from the United States. Pedigrees of the French, Spanish, African and Malaysian families are shown in Figure 1.…”

“…1 Though HED has been described in families of various ethnic origins, [2][3][4][5][6] it is particularly common in families of French Canadian origin suggesting a founder effect for the HED mutation in this population. [7][8][9] Interestingly, HED occurs predominantly in south-west Quebec, a region quite distinct from the north-east part of the province where all previous founder effects have been found.…”

“…9 Later studies have confirmed linkage of HED to this region in an ethnically diverse group of families (Indian, French and Scottish-Irish), demonstrating absence of genetic heterogeneity in HED. 5,6 As a step towards the identification of the HED gene, a radiation hybrid map of 48 loci on chromosome 13q including the HED locus was constructed and eight new polymorphic markers were isolated in the candidate region. 11 In the current study, we genotype an extended panel of 29 HED families of various ethnic origins with a set of 10 polymorphic markers to study genetic homogeneity in HED and finely map the HED gene.…”