Premium
Bohring‐Opitz syndrome caused by an ASXL1 mutation inherited from a germline mosaic mother
Author(s) -
Bedoukian Emma,
Copenheaver Deborah,
Bale Sherri,
Deardorff Matthew
Publication year - 2018
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38686
Subject(s) - frameshift mutation , exome sequencing , genetics , germline mosaicism , nonsense mutation , biology , germline , exome , microcephaly , proband , germline mutation , mutation , failure to thrive , missense mutation , gene
Bohring‐Opitz syndrome (BOS) is characterized clinically by severe developmental delays, microcephaly, failure to thrive, and characteristic facial features (prominent eyes, facial nevus simplex [flammeus], and others). Most patients meeting the clinical criteria for BOS (MIM: 605039) have a de novo nonsense or frameshift variant in ASXL 1. We report a case of BOS caused by a pathogenic ASX L1 variant inherited from a germline mosaic mother. The ASX L1 mutation was detected via trio exome sequencing. The sequencing data demonstrated that the variant was inherited maternally but that the maternal variant was underrepresented in comparison to the normal allele. These results suggested maternal mosaicism for the variant. Additional testing on the mother was performed on buccal cell DNA, which was also consistent with mosaicism. The mother had been reported to be healthy and the family history is unremarkable. This is the first report of BOS caused by a mutation inherited from an unaffected, presumed germline mosaic parent. This phenomenon has been reported for other traditionally de novo dominant disorders like CHARGE syndrome and Cornelia de Lange syndrome. This case emphasizes the need for accurate low but non‐negative recurrence risk counseling for families with children with BOS and it impacts exome interpretation strategy.