Premium
Whole exome sequencing diagnoses the first fetal case of B ainbridge‐ R opers syndrome presenting as pontocerebellar hypoplasia type 1
Author(s) -
Bacrot Séverine,
Mechler Charlotte,
Talhi Naima,
MartinCoignard Dominique,
Roth Philippe,
Michot Caroline,
Ichkou Amale,
Alibeu Olivier,
Nitschke Patrick,
Thomas Sophie,
Vekemans Michel,
Razavi Férechté,
Boutaud Lucile,
AttieBitach Tania
Publication year - 2018
Publication title -
birth defects research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.845
H-Index - 17
ISSN - 2472-1727
DOI - 10.1002/bdr2.1191
Subject(s) - exome sequencing , hypoplasia , mutation , genetics , phenotype , medicine , prenatal diagnosis , global developmental delay , biology , fetus , gene , anatomy , pregnancy
Background Bainbridge‐Ropers syndrome (BRPS) is a recently identified severe disorder characterized by failure to thrive, facial dysmorphism, and severe developmental delay, caused by de novo dominant loss of function mutation in the ASXL3 gene. Case We report here the first case of prenatal BRPS in a fetus presenting with arthrogryposis on ultrasound and for pontocerebellar hypoplasia type 1 (PCH1) following neuropathological examination. The diagnosis was done by whole exome sequencing that identified a novel de novo ASXL3 mutation. We review 29 previous published cases. Discussion The fetopathological examination allowed to extend the phenotype to central nervous system and the genetic study highlights ASXL3 as a dominant gene responsible for PCH1 phenotype. Recognizing heterozygous ASXL3 mutation as a cause of prenatal PCH1 is essential for both large scale molecular analysis in the NGS era and genetic counseling.