Dyssegmental dysplasia Rolland –Desbuquois type is caused by pathogenic variants in HSPG2 - a founder haplotype shared in five patients

AbstractDyssegmental dysplasia (DD) is a severe skeletal dysplasia comprised of two subtypes: lethal Silverman –Handmaker type (DDSH) and nonlethal Rolland–Desbuquois type (DDRD). DDSH is caused by biallelic pathogenic variants inHSPG2 encoding perlecan, whereas the genetic cause of DDRD remains undetermined. Schwartz –Jampel syndrome (SJS) is also caused by biallelic pathogenic variants inHSPG2 and is an allelic disorder of DDSH. In SJS and DDSH, 44 and 8 pathogenic variants have been reported inHSPG2, respectively. Here, we report that five patients with DDRD carried four pathogenic variants inHSPG2: c.9970  G >  A (p.G3324R), c.559 C >  T (p.R187X), c7006 + 1 G >  A, and c.11562 + 2 T >  G. Two patients were homozygous for p.G3324R, and three patients were heterozygous for p.G3324R. Haplotype analysis revealed a founder haplotype spanning 85,973 bp shared in the five patients. SJS, DDRD, and DDSH are allelic disorders with pathogenic variants inHSPG2.

Source: Journal of Human Genetics - February 29, 2024 Category: Genetics & Stem Cells Source Type: research