Bohring-Opitz syndrome caused by an ASXL1 mutation inherited from a germline mosaic mother.
Emma C BedoukianDeborah CopenheaverSherri BaleMatthew DeardorffPublished in: American journal of medical genetics. Part A (2019)
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 ASXL1. We report a case of BOS caused by a pathogenic ASXL1 variant inherited from a germline mosaic mother. The ASXL1 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.
Keyphrases
- single cell
- case report
- dna repair
- zika virus
- ejection fraction
- copy number
- young adults
- optical coherence tomography
- cell therapy
- mesenchymal stem cells
- dna damage
- early onset
- intellectual disability
- bone marrow
- pregnant women
- autism spectrum disorder
- smoking cessation
- cell free
- circulating tumor cells
- preterm birth
- weight loss
- human immunodeficiency virus
- men who have sex with men
- hepatitis c virus