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

Molecular Syndromology

Hicham Zerhouni¹  Véronique Pingault¹  Siham C. Elalaoui¹  Abdelaziz Sefiani¹  Ilham Ratbi¹  Mohamed Azouz¹  Yassamine Doubaj¹  Fouad Ettayebi¹ 

[1] aDépartement de Génétique Médicale, Institut National d'Hygiène, France

关键词: EDNRB;    Moroccan;    Novel mutation;    Shah-Waardenburg syndrome;   

DOI  :  10.1159/000371590

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

Unknown