The Central Laboratory of Birth Defects Prevention and Control, Ningbo Women and Children's Hospital, Ningbo, Zhejiang, 315000, China.
Department of Obstetrics, Ningbo Women and Children's Hospital, Ningbo, Zhejiang, 315000, China.
BMC Med Genomics. 2023 Aug 17;16(1):190. doi: 10.1186/s12920-023-01631-7.
Rhizomelic limb shortening with dysmorphic features (RLSDF) has already been a disorder of the rare autosomal recessive skeletal dysplasia, just having a few reported cases. RLSDF is caused by protein kinase domain containing, cytoplasmic(PKDCC)gene variants. In this study, we describe the clinical features and potential RLSDF molecular etiology in a fetus from China.
Genomic DNA (gDNA) extracted from the fetal muscle tissue and parents' peripheral blood was subjected to chromosomal microarray analysis (CMA) and trio-based whole exome sequencing (Trio-WES). The candidate pathogenic variants were verified by using Sanger sequencing.
Trio-WES identified two compound heterozygous variants in PKDCC, c.346delC (p.Pro117Argfs*113) and c.994G > T (p.Glu332Ter), inherited from the father and mother, respectively. Both variants are classified as pathogenic according to American College of Medical Genetics and Genomics guidelines.
We reported the first prenatal case of RLSDF caused by PKDCC in the Chinese population. Our findings extended the variation spectrum of PKDCC and emphasized the necessity of WES for the early diagnosis of skeletal dysplasia and other ultrasound structural abnormalities in fetuses.
肢端骨干发育不良伴发育异常（RLSDF）已成为一种罕见的常染色体隐性骨骼发育不良疾病，仅有少数病例报道。RLSDF 是由蛋白激酶结构域包含、细胞质（PKDCC）基因突变引起的。本研究描述了来自中国的一个胎儿的临床特征和潜在的 RLSDF 分子病因。
从胎儿肌肉组织和父母外周血中提取基因组 DNA（gDNA），进行染色体微阵列分析（CMA）和基于 trio 的全外显子组测序（Trio-WES）。通过 Sanger 测序验证候选致病变异。
trio-WES 在 PKDCC 中发现了两个复合杂合变异，c.346delC（p.Pro117Argfs*113）和 c.994G>T（p.Glu332Ter），分别来自父亲和母亲。根据美国医学遗传学与基因组学学院的指南，这两种变异均被归类为致病性变异。
我们报道了首例中国人 PKDCC 引起的 RLSDF 产前病例。我们的发现扩展了 PKDCC 的变异谱，并强调了 WES 对于胎儿骨骼发育不良和其他超声结构异常的早期诊断的必要性。
