Clefting disorders

Gene: FST

Red List (low evidence)

In a cohort of 72 families with orofacial clefting, Cox et al. (2019) performed exome sequencing and identified a father and 2 daughters (family 22) with cleft lip and palate who were heterozygous for missense variant (C56Y) in FST. A highly conserved residue within the 63-residue N-terminal domain. The variant was not found in the unaffected paternal grandmother or in the gnomAD database. Classed as a VUS. Functional analysis in transfected HEK293T cells, using a stable cell line sensitive to stimulation by the FST downstream target GDF11, demonstrated that wildtype FST efficiently and completely antagonized GDF11-stimulated reporter activity. In contrast, the C56Y mutant did not significantly inhibit the stimulation of reporter activity, regardless of the amount of mutant vector transfected.
Sources: Expert list

Created: 1 Feb 2021, 1:41 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
orofacial clefting

Publications

• PubMed: 31215115