A Japanese patient with RAD51‐associated Fanconi anemia
- 25 March 2019
- journal article
- research article
- Published by Wiley in American Journal of Medical Genetics Part A
- Vol. 179 (6), 900-902
- https://doi.org/10.1002/ajmg.a.61130
Abstract
RAD51 is the only identified autosomal dominant gene to date causative of Fanconi anemia (FA) due to dominant negative effects. Only two patients with RAD51‐associated FA have been reported with atypical FA phenotypes without bone marrow failure. We describe a new Asian patient with a novel RAD51 mutation, presenting with multiple congenital anomalies and atypical FA with chromosomal instability. The patient was a 9‐year‐old Japanese girl. She had strabismus, myopia, submucous cleft palate, bilateral hearing impairment, and scoliosis. She also had growth retardation, developmental delay, and severe intellectual disability. We performed trio whole exome sequencing and Sanger sequencing and identified a de novo RAD51 mutation (c.725A>G, p.Gln242Arg). Isolated lymphocytes from the patient were hypersensitive to chromosomal breakage induced by the DNA cross‐linking agent, mitomycin C. Our detailed phenotypic analysis of the RAD51‐associated atypical FA revealed clinical manifestations from the diverse population and a consistent FA phenotype characterized by chromosome instability, intellectual disability, radial ray abnormality, and microcephaly, but not bone marrow failure.Keywords
Funding Information
- Japan Agency for Medical Research and Development
- Japan Agency for Medical Research and Development
This publication has 5 references indexed in Scilit:
- ANKRD11 variants cause variable clinical features associated with KBG syndrome and Coffin–Siris-like syndromeJournal of Human Genetics, 2017
- A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51Nature Communications, 2015
- A Dominant Mutation in Human RAD51 Reveals Its Function in DNA Interstrand Crosslink Repair Independent of Homologous RecombinationMolecular Cell, 2015
- RAD51 Haploinsufficiency Causes Congenital Mirror Movements in HumansAmerican Journal of Human Genetics, 2012
- Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombinationNature Structural & Molecular Biology, 2010