罗伦-德斯布奎斯型节段性发育不良是由 HSPG2 中的致病变异引起的 - 五个患者中共享的一个创始单倍型。
Dyssegmental dysplasia Rolland-Desbuquois type is caused by pathogenic variants in HSPG2 - a founder haplotype shared in five patients.
机构信息
Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Division of Clinical Genetics, Hokkaido University Hospital, Sapporo, Japan.
出版信息
J Hum Genet. 2024 Jun;69(6):235-244. doi: 10.1038/s10038-024-01229-6. Epub 2024 Feb 29.
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.
节段性发育不良（DD）是一种严重的骨骼发育不良，包括两种亚型：致死性 Silverman-Handmaker 型（DDSH）和非致死性 Rolland-Desbuquois 型（DDRD）。DDSH 是由编码硫酸乙酰肝素蛋白聚糖 2（perlecan）的 HSPG2 双等位基因致病性变异引起的，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的，是 DDSH 的等位基因疾病。在 SJS 和 DDSH 中，HSPG2 分别报道了 44 种和 8 种致病性变异。在这里，我们报告了五例 DDRD 患者携带 HSPG2 中的四个致病性变异：c.9970G>A（p.G3324R）、c.559C>T（p.R187X）、c7006+1G>A 和 c.11562+2T>G。两名患者为 p.G3324R 纯合子，三名患者为 p.G3324R 杂合子。单体型分析显示，五个患者共享一个跨越 85973bp 的致病变异的创始人单体型。SJS、DDRD 和 DDSH 是由 HSPG2 中的致病性变异引起的等位基因疾病。
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