Severe microcephaly

Gene: FBRSL1

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

Created: 10 Mar 2022, 10:52 a.m. | Last Modified: 10 Mar 2022, 10:52 a.m.

Panel Version: 2.282

Green List (high evidence)

Comment on list classification: There is enough evidence to promote this gene to Green at the next GMS panel update (added 'for-review' tag) - sufficient number of unrelated cases with distinct variants and relevant phenotype, supported by functional data.

Created: 22 Jan 2021, 2:54 p.m. | Last Modified: 22 Jan 2021, 2:54 p.m.

Panel Version: 2.76

Currently not associated with any phenotype in OMIM or Gene2Phenotype.

- PMID: 32424618 (2020): Three different de novo truncating variants identified by WES in three unrelated individuals with a congenital malformation syndrome. Clinical characteristics include respiratory insufficiency, postnatal growth restriction, microcephaly, ID/GDD and other malformations. 2/3 had heart defects, cleft palate and hearing impairment.

Knockdown of Fbrsl1 in Xenopus laevis embryos resulted in disturbance in the outgrowth of cranial nerves and motor neurons, and craniofacial abnormalities which were rescued with the short N-terminal isoform but not with the isoform bearing one of the human variants.
Sources: Literature

Created: 22 Jan 2021, 2:53 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability; Microcephaly; Heart defect; Cleft palate; Contractures; Hearing impairment; Skin creases

Publications

• 32424618