A Novel Mutation in the Endothelin B Receptor Gene in a Moroccan Family with Shah-Waardenburg Syndrome

Abstract

Waardenburg syndrome (WS) is a neurocristopathy disorder combining sensorineural deafness and pigmentary abnormalities. The presence of additional signs defines the 4 subtypes. WS type IV, also called Shah-Waardenburg syndrome (SWS), is characterized by the association with congenital aganglionic megacolon (Hirschsprung disease). To date, 3 causative genes have been related to this congenital disorder. Mutations in the EDNRB and EDN3 genes are responsible for the autosomal recessive form of SWS, whereas SOX10 mutations are inherited in an autosomal dominant manner. We report here the case of a 3-month-old Morrocan girl with WS type IV, born to consanguineous parents. The patient had 3 cousins who died in infancy with the same symptoms. Molecular analysis by Sanger sequencing revealed the presence of a novel homozygous missense mutation c.1133A>G (p.Asn378Ser) in the EDNRB gene. The proband's parents as well as the parents of the deceased cousins are heterozygous carriers of this likely pathogenic mutation. This molecular diagnosis allows us to provide genetic counseling to the family and eventually propose prenatal diagnosis to prevent recurrence of the disease in subsequent pregnancies.

Biology of human melanocyte development, Piebaldism, and Waardenburg syndrome

“…SOX 10, EDN 3, and EDNRB , in addition to the melanocyte neural crest‐derived cells, are critical genes for enteric neural crest‐derived cell proliferation, migration, and survival. Mutations in any of these three genes can result in the absence of melanocytes and neurons in the skin and gut, respectively…”

The first Korean case of Waardenburg-Shah syndrome with novel endothelin receptor type B mutations

“…Mutations in EDNRB or EDN3 genes are found in 20% to 30% of WS type IV patients [7]. The EDNRB gene, located in 13q22.3, spans 24 kb and comprises 7 exons [8].…”

Untitled

“…Three putative genes have been identified including EDNRB, EDN3 and SOX10 [5]. Although the prevalence is ill-defined, about 50 cases had been reported till 2015 [6].…”