Mutation in the ED1 Gene, Ala349Thr, in a Korean Patient with X‐Linked Hypohidrotic Ectodermal Dysplasia Developing de novo

Abstract

Hypohidrotic ectodermal dysplasia (HED) is a very rare disease characterized by the virtual absence of eccrine glands, dry skin, scanty hair, and dental abnormalities. It is transmitted by an X-linked recessive gene or rarely an autosomal recessive gene. Therefore it is only males who fully express the condition. It is caused by mutations within the ED1 gene, which encodes a protein, ectodysplasin-A (EDA). Typically there is frontal bossing, saddle nose, pointed chin, a prominent supraorbital ridge with periorbital hyperpigmentation, and absence of teeth. Those affected show great intolerance to heat. In the current absence of effective treatment for many hereditary skin diseases, comprehensive, accurate prenatal or postnatal genetic counseling can provide information to parents at risk of having affected children. We report HED in a 6-year-old boy with an Ala349Thr (GCA --> ACA) missense mutation developed de novo. Both parents and a 16-week gestational age fetus were healthy. We thought direct sequencing analysis for the ED1 gene using peripheral blood or amniotic fluid was preferable for an accurate diagnosis of this disease, although there was some risk of not detecting the mutation. After the results of this study were communicated to the parents, the mother was freed of her guilty feelings of the past 6 years and has now delivered a healthy male infant.

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

“…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.…”

Dento-Craniofacial Phenotypes and underlying Molecular Mechanisms in Hypohidrotic Ectodermal Dysplasia (HED): a Review

“…In the permanent dentition, this clinical feature could suggest an EDA mutation in 1/500 cases (Spfaer, 1981). Oligodontia in the primary dentition appears to be an important clinical predictor sign of the EDA mutation in females (Na et al, 2004). These dental phenotypic manifestations thus play a crucial role in the detection and diagnosis of EDA mutation female carriers and should lead to further clinical, radiographic, and molecular investigation.…”

X-Linked Hypohidrotic Ectodermal Dysplasia: New Features and a Novel <b><i>EDA</i></b> Gene Mutation

“…XLHED is known to be caused by mutations in the ectodysplasin-A ( EDA ) gene, located at Xq12q13.1, which encodes a transmembrane protein expressed by keratinocytes, hair follicles, and sweat glands, possibly having a key role in epithelial-mesenchymal signaling [Kere et al, 1996;Na et al, 2004]. In a few cases, HED may present as an autosomal recessive or a dominant disorder linked to mutations in the EDA receptor ( EDAR ) or in the EDARassociated death domain ( EDARADD ).…”