Protein arginine N-methyltransferase 7 (PRMT7) encodes an arginine methyltransferase central to a number of fundamental biological processes, mutations in which result in an autosomal recessive developmental disorder characterized by short stature, brachydactyly, intellectual developmental disability and seizures (SBIDDS). To date, fewer than 15 patients with biallelic mutations in PRMT7 have been documented. Here we report brothers from a consanguineous Iraqi family presenting with a developmental disorder characterized by global developmental delay, shortened stature, facial dysmorphisms, brachydactyly, and kidney dysfunction. In both affected brothers, whole genome sequencing (WGS) identified a novel homozygous substitution in PRMT7 (ENST00000339507.5), c.1097 G > A (p.Cys366Tyr), considered to account for the majority of the phenotypic presentation. Rare compound heterozygous mutations in the dysplasia-associated perlecan-encoding HSPG2 gene (ENST00000374695.3) were also found (c.10721-2dupA, p.Ser71Asn and c.212 G > A), potentially accounting for the kidney dysfunction. In addition to expanding the known mutational spectrum of variably expressive PRMT7 mutations alongside potential digenic inheritance with HSPG2, this report underlines the diagnostic utility of a WGS-guided analysis in the detection of rare genetic disorders.

蛋白精氨酸 N-甲基转移酶 7 ( PRMT7 ) 编码一种精氨酸甲基转移酶，该酶对许多基本生物学过程至关重要，突变会导致常染色体隐性遗传发育障碍，其特征是身材矮小、短指、智力发育障碍和癫痫发作 (SBIDDS)。迄今为止，记录在案的PRMT7 双等位基因突变患者不到 15 例。在这里，我们报告了一个伊拉克近亲家庭的兄弟，他们患有发育障碍，其特征是整体发育迟缓、身材矮小、面部畸形、短指畸形和肾功能障碍。在两个受影响的兄弟中，全基因组测序 (WGS) 在PRMT7中发现了一个新的纯合子替换(ENST00000339507.5)，c.1097 G > A (p.Cys366Tyr)，被认为占表型表现的大部分。还发现了发育异常相关的珍珠聚糖编码HSPG2基因 (ENST00000374695.3) 中罕见的复合杂合突变(c.10721-2dupA、p.Ser71Asn 和 c.212 G > A)，这可能是肾功能障碍的原因。除了扩大可变表达PRMT7突变的已知突变谱以及HSPG2的潜在双基因遗传外，本报告还强调了 WGS 引导分析在检测罕见遗传疾病中的诊断效用。