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

Abstract

Hypohidrotic ectodermal dysplasia (HED) is characterized by severe hypohidrosis, hypotrichosis, and hypodontia. It can be inherited in autosomal dominant, autosomal recessive, or X-linked patterns. Mutations in the EDA gene, which encodes ectodysplasin-A, are responsible for X-linked HED (XLHED).In the present study, we identified a Chinese Han family with XLHED. Direct DNA sequence analysis of the entire coding region and exon-intron boundaries of EDA identified a novel de novo mutation, c.573_574insT, in two affected males and one carrier female. Restriction fragment length polymorphism (RFLP) analysis showed that the mutation was not present in 200 controls. The 1-bp insertion mutation resulted in a frameshift, which causes premature termination of EDA polypeptide and truncation of the EDA protein. These results suggest that the c.573_574insT mutation of the EDA gene is a cause for XLHED in the family. To the best of our knowledge, this is the first de novo insertion mutation of EDA described for XLHED.Keywords EDA Á Frameshift mutation Á RFLP Á X-linked hypohidrotic ectodermal dysplasia IntroductionHypohidrotic ectodermal dysplasia (HED) is found to occur worldwide, with an estimated incidence of 1 per 100,000 births (Zonana 1993). Ectodermal dysplasias typically affect the hair, teeth, nails, and/or skin. HED is primarily characterized by the partial or complete absence of certain sweat glands (eccrine glands), causing the lack of or diminished sweating (anhidrosis or hypohidrosis), heat intolerance, and fever, abnormally sparse hair (hypotrichosis), and the absence (anodontia or hypodontia) and/or malformation of certain teeth. It can be inherited in autosomal dominant, autosomal recessive, or X-linked patterns. However, X-linked HED (XLHED; OMIM 305100) Changzheng Huang and Qinbo Yang contribute equally to this work.

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

“…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.…”

“…The primer sequences and PCR conditions were performed as previously described (Huang et al, 2006). PCR-amplified fragments were purified using the spin column PCR products purification kit (Bio Basic Inc., Markham Ontario, Canada) and were visualized on 2% agarose gels to check for their purity and correct sizes.…”

Identification of a novel mutation of the EDA gene in X-linked hypohidrotic ectodermal dysplasia

“…This domain is located at the C-terminal end of the protein and is composed of 10 predicted antiparallel β-sheets, which are necessary for the binding of EDA to EDAR (Ezer et al, 1999). The recognition and interaction between EDA and EDAR may activate the nuclear factor-kB and c-Jun N-terminal kinase pathways involved in the regulation of ectodermal morphogenesis (Huang et al, 2006). Here, we describe the clinical features and molecular characterization of a novel point mutation in the EDA gene in a Chinese family with XLHED ( Figure 1).…”