Endocrinology Department, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030012, P.R. China.
Mol Med Rep. 2019 Sep;20(3):2373-2380. doi: 10.3892/mmr.2019.10464. Epub 2019 Jul 3.
The aim of the present study was to determine the mutant genes and mutation sites in a family with maturity‑onset diabetes of the young (MODY), in order to provide evidence for the diagnosis and treatment of clinical MODY. Based on the clinical characteristics of MODY, one family was selected from the Department of Endocrinology of Shanxi Provincial People's Hospital (Shanxi, China). The family comprised seven individuals, four of which were healthy (without MODY), and the whole exome of the individual with MODY, her father and her mother were sequenced. A suspected case (patient's uncle) and a healthy individual (patient's aunt) were sequenced for verification. The Q30 ratio was >90% in the family of three and the sequencing quality was good. The alignment rate was >95%, while the repeat sequence was <10%, with a mean sequencing depth of >120x, which is sufficient to identify mutations. According to Mutation Taster and LRT, it was predicted that the p.leu73Pro mutation of the pancreatic and duodenal homeobox 1 (PDX1) gene was deleterious. The mutation was verified by next‑generation sequencing as the pathogenic site in this family. In conclusion, a novel mutation site of MODY type 4 in the PDX1 gene was identified in a family with MODY, which may provide a basis for its clinical treatment. Whole‑exome sequencing appears to be of assistance in accurately diagnosing MODY.
本研究旨在确定一个年轻起病的成年型糖尿病（MODY）家系中的突变基因和突变位点，为临床 MODY 的诊断和治疗提供依据。根据 MODY 的临床特征，从山西省人民医院内分泌科选择了一个家系，该家系包括 7 个人，其中 4 人健康（无 MODY），对 MODY 个体、其父亲和母亲的全外显子进行了测序。对一个疑似病例（患者的叔叔）和一个健康个体（患者的姑姑）进行了测序验证。在 3 名家系成员中，Q30 比值>90%，测序质量良好。比对率>95%，重复序列<10%，平均测序深度>120x，足以识别突变。根据 Mutation Taster 和 LRT，预测胰腺十二指肠同源盒 1（PDX1）基因的 p.leu73Pro 突变是有害的。通过下一代测序验证了该突变是该家系中的致病位点。总之，在一个 MODY 家系中发现了 PDX1 基因 MODY 型 4 的一个新突变位点，这可能为其临床治疗提供依据。全外显子组测序似乎有助于准确诊断 MODY。
