Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, 361005, Fujian, China.
Reproductive Medicine Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, China.
BMC Med Genet. 2019 Aug 1;20(1):133. doi: 10.1186/s12881-019-0864-1.
Proximal symphalangism (SYM1; OMIM 185800), also called Cushing's symphalangism, is an infrequent autosomal dominant disease. An SYM1 patient typically features variable fusion of proximal interphalangeal joints in the hands and feet.
We recruited a four-generation Chinese non-consanguineous family with SYM1. We examined their hands and feet using X-rays to confirm fusion of proximal interphalangeal joints. We evaluated their audiology using standard audiometric procedures and equipment. Then, we identified genetic variants using whole exome sequencing and validated mutations using Sanger sequencing. Mutation pathogenicity was analyzed with bioinformatics.
Radiographs revealed proximal-joint fusion of fingers and toes in the patients. Two elderly individuals (II:1 and II:4) exhibited slight hearing loss. Additionally, we detected a novel heterozygous missense mutation in exon 1 of NOG (NM_005450) c.124C > T, p.(Pro42Ser) in all patients. This c.124C > T mutation is highly conserved across multiple species and the p.(Pro42Ser) variation is potentially highly pathogenic.
Our results suggest that heterozygous c.124C > T, p.(Pro42Ser) in NOG is a novel mutation that causes human SYM1 phenotype.
近侧指（趾）间关节融合症（SYM1；OMIM 185800），也称 Cushing 近侧指（趾）间关节融合症，是一种罕见的常染色体显性遗传病。SYM1 患者的典型特征是手足近侧指间关节的融合具有可变性。
我们招募了一个有 SYM1 的四代中国非近亲家族。我们使用 X 射线检查他们的手和脚，以确认近侧指间关节的融合。我们使用标准听力测试程序和设备评估他们的听力。然后，我们通过全外显子组测序确定遗传变异，并通过 Sanger 测序验证突变。使用生物信息学分析突变的致病性。
X 光片显示患者手指和脚趾的近关节融合。两名年长的个体（II:1 和 II:4）表现出轻微的听力损失。此外，我们在所有患者中检测到 NOG（NM_005450）exon 1 中的杂合错义突变 c.124C > T，p.（Pro42Ser）。这个 c.124C > T 突变在多个物种中高度保守，而 p.（Pro42Ser）变异很可能具有高度致病性。
我们的结果表明，NOG 中的杂合 c.124C > T，p.（Pro42Ser）是导致人类 SYM1 表型的一种新突变。
