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.

节段发育不良 (DD) 是一种严重的骨骼发育不良，由两种亚型组成：致死性 Silverman-Handmaker 型 (DDSH) 和非致死性 Rolland-Desbuquois 型 (DDRD)。 DDSH 是由编码基底蛋白聚糖的HSPG2中的双等位基因致病变异引起的，而 DDRD 的遗传原因尚未确定。 Schwartz-Jampel 综合征 (SJS) 也是由HSPG2的双等位基因致病性变异引起，是 DDSH 的等位基因疾病。在SJS和DDSH中， HSPG2分别报道了44个和8个致病变异。在此，我们报告 5 名 DDRD 患者在HSPG2中携带四种致病性变异：c.9970 G > A (p.G3324R)、c.559 C > T (p.R187X)、c7006 + 1 G > A 和 c.559 C > T (p.R187X)。 11562 + 2 T > G。两名患者为 p.G3324R 纯合子，三名患者为 p.G3324R 杂合子。单倍型分析揭示了 5 名患者共有一个跨越 85,973 bp 的创始人单倍型。 SJS、DDRD 和 DDSH 是HSPG2具有致病性变异的等位基因疾病。