Dyssegmental dysplasia Rolland-Desbuquois type is caused by pathogenic variants in HSPG2 - a founder haplotype shared in five patients.
J Hum Genet
; 69(6): 235-244, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38424183
ABSTRACT
Dyssegmental 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 in HSPG2 encoding perlecan, whereas the genetic cause of DDRD remains undetermined. Schwartz-Jampel syndrome (SJS) is also caused by biallelic pathogenic variants in HSPG2 and is an allelic disorder of DDSH. In SJS and DDSH, 44 and 8 pathogenic variants have been reported in HSPG2, respectively. Here, we report that five patients with DDRD carried four pathogenic variants in HSPG2 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 in HSPG2.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteocondrodisplasias
/
Haplótipos
/
Proteoglicanas de Heparan Sulfato
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article