Severe microcephaly

Gene: RAD51

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 10 Mar 2022, 1:37 p.m. | Last Modified: 10 Mar 2022, 1:37 p.m.

Panel Version: 2.292

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - 3 unrelated cases with relevant phenotype and different de novo variants. Phenotype-gene relationship listed in OMIM (MIM# 617244).

Created: 13 Oct 2021, 4:05 p.m. | Last Modified: 13 Oct 2021, 4:05 p.m.

Panel Version: 2.264

Three unrelated patients have been identified to date (PMIDs: 26681308; 26253028; 30907510) with an atypical FA phonotype involving chromosomal instability without bone marrow failure or malignancies along with private heterozygous variants (c.877G>A; c.391A>C; c.725A>G) in the RAD51 gene. Variants occurred de novo with a dominant negative effect. All three individuals presented with thumb and radial abnormalities, microcephaly, and DD/ID (third patient showed early DD but above average IQ by age 13); and two individuals also had growth retardation (probable in third case but not reported on) and hearing impairment.
Sources: Literature

Created: 13 Oct 2021, 4:02 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Fanconi anemia, complementation group R, OMIM:617244

Publications

• 26681308
• 26253028
• 30907510