title: 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.
authors: Département de Génétique Médicale, Institut National d'Hygiène, France ; Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, France.
authors: Yassamine
authors: Y
authors: Doubaj
authors: Département de Génétique, AP-HP, Hôpital Henri Mondor, Créteil, France.
authors: Véronique
authors: V
authors: Pingault
authors: Département de Génétique Médicale, Institut National d'Hygiène, France ; Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, France.
authors: Siham C
authors: SC
authors: Elalaoui
authors: Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, France.
authors: Ilham
authors: I
authors: Ratbi
authors: Service des Urgences Chirurgicales Pédiatriques, Hôpital d'Enfants, Rabat, Morocco, France.
authors: Mohamed
authors: M
authors: Azouz
authors: Service des Urgences Chirurgicales Pédiatriques, Hôpital d'Enfants, Rabat, Morocco, France.
authors: Hicham
authors: H
authors: Zerhouni
authors: Service des Urgences Chirurgicales Pédiatriques, Hôpital d'Enfants, Rabat, Morocco, France.
authors: Fouad
authors: F
authors: Ettayebi
authors: Département de Génétique Médicale, Institut National d'Hygiène, France ; Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, France.
authors: Abdelaziz
authors: A
authors: Sefiani
keywords: EDNRB; Moroccan; Novel mutation; Shah-Waardenburg syndrome