A novel missense mutation of the EDA gene in a Mongolian family with congenital hypodontia

Abstract

X-linked hypohidrotic ectodermal dysplasia (HED) is a rare disease characterized by the hypoplasia or absence of eccrine glands, dry skin, scant hair, and dental abnormalities. Here, we report a Mongolian family with congenital absence of teeth inherited in an X-linked fashion. The affected members of the family did not show other HED characteristics, except hypodontia. We successfully mapped the affected locus to chromosome Xq12-q13.1, and then found a novel missense mutation, c.193C>G, in the ectodysplasin A (EDA) gene in all affected males and carrier females. The mutation causes arginine to be replaced by glycine in codon 65 (R65G) in the juxtamembrane region of EDA.In addition, 33% (3/9) of female carriers have a skewed X-chromosome inactivation pattern. Our result strongly suggests that the c.193C>G mutation is the diseasecausing mutation in this family.

Missense mutation of the EDA gene in a Jordanian family with X-linked hypohidrotic ectodermal dysplasia: phenotypic appearance and speech problems

“…In the obligate carriers (heterozygous), mother and sister, mild to moderate symptoms of the disease were observed confirming X-linked inheritance. This is consistent with most studies (Monreal et al, 1998;Sekiguchi et al, 2005;Tao et al, 2006;Vinolo et al, 2006). However, in some families, the carriers do not exhibit any clinical phenotype, suggesting phenotypic heterogeneity of this disease (Huang et al, 2006).…”

“…In addition, XLHED may have emotional consequences for affected individuals at an early age (Yavuz et al, 2006). The clinical findings of the affected male in the family examined fall within the scope of previous reports showing defective development of hair, teeth, nails, and skin Chao et al, 2003;Lin et al, 2004;Na et al, 2004;Huang et al, 2006;Tao et al, 2006;Tariq et al, 2007;Fan et al, 2008). The defect in speech in the affected male could be due to the presence of the large diastema between the central incisors and the maladaptation in the production of the fricative sibilants (Sharma et al, 1978).…”

“…Mutations in any of these domains were reported to produce XLHED (Bayes et al, 1998;Ezer et al, 1999;Vincent et al, 2001;Chao et al, 2003). These mutations include small and large deletions (Vincent et al, 2001;Lin et al, 2004), frameshifts (Huang et al, 2006), insertions (Huang et al, 2006;Tariq et al, 2007) and substitution (Paakkonen et al, 2001;Na et al, 2004;Sekiguchi et al, 2005;Tao et al, 2006;Fan et al, 2008). The mutation described in this study is located in the amino terminal, extracellular domain, an essential hydrophilic domain required for proper function of ectodysplasin-A.…”

“…XLHED is characterized by reduced sweating (anhidrosis) and heat intolerance, sparse hair (hypotrichosis), and the absence of certain teeth (oligodontia or hypodontia) (Kupietzky and Houpt, 1995;Park et al, 1999). Hemizygous males show severe forms of the disease, while heterozygous females often manifest mild to moderate symptoms because of X-chromosome inactivation (Monreal et al, 1998;Vincent et al, 2001;Sekiguchi et al, 2005;Tao et al, 2006). XLHED is caused by mutations in the EDA gene (Kere et al, 1996;Bayes et al, 1998), which encodes ectodysplasin-A.…”

A novel de novo frame-shift mutation of the EDA gene in a Chinese Han family with hypohidrotic ectodermal dysplasia

“…Recently, one novel R65G mutation in the EDA gene was identified in a Mongolian family with only hypodontia, and without other HED manifestations (Tao et al 2006), whereas another mutation G291R was reported in a Japanese family with hypohidrosis, hypotrichosis, and hypodontia (with only a primary central incisor and a permanent central incisor bud in the maxilla) (Sekiguchi et al 2005), suggesting phenotypic heterogeneity of this syndrome. It is interesting to note that heterozygous mutation carriers of XLHED may have variable clinical features, displaying minor or moderate degrees of hypodontia, hypotrichosis, and hypohidrosis.…”