Quantitative hypermorphic FAM111A alleles cause autosomal recessive Kenny-Caffey syndrome type 2 and osteocraniostenosis.

ABSTRACT: Kenny-Caffey syndrome (KCS) is a rare genetic disorder characterized by extreme short stature, cortical thickening and medullary stenosis of tubular bones, facial dysmorphism, abnormal T cell function, and hypoparathyroidism. Biallelic loss-of-function variants in TBCE cause autosomal recessive type 1 KCS (KCS1). By contrast, heterozygous missense variants in a restricted region of the FAM111A gene have been identified in autosomal dominant type 2 KCS (KCS2) and a more severe lethal phenotype, osteocraniostenosis (OCS); these variants have recently been shown to confer a gain of function. In this study, we describe 2 unrelated children with KCS and OCS who were homozygous for different FAM111A variant alleles that result in replacement of the same residue, Tyr414 (c.1241A>G, p.Y414C and c.

SUBMITTER: Li D 

PROVIDER: S-EPMC11949059 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature