National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory For Metabolic Bone Diseases, and Department of Endocrinology and Metabolism, the Second XiangYa Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
Endocrine. 2021 Jul;73(1):37-46. doi: 10.1007/s12020-021-02682-5. Epub 2021 Mar 20.
17q12 Deletion Syndrome is heterogeneous and the reasons remain unclear. We clarified the clinical characteristics of adulthood diabetes onset 17q12 deletion syndrome and investigated the unclear phenotype-genotype correlation.
We collected the clinical history and laboratory results of a family with autosomal dominant inheritance diabetes and renopathy. Sanger sequencing of HNF1B and a panel of monogenic diabetic genes were performed to identify the monogenetic diabetes. Semiquantitative PCR and Chromosome 100 K sequence analysis were performed to analyze the copy numbers variation of diabetes related genes. Allelic specific quantitative PCR were used for TBC1D3 and paralogues diagnosis. The reported cases were reviewed and assessed to compare with patients in this study.
Differential variants in genomic DNA and clinical presentations among family members were explored to determine the probable phenotype-genotypes correlation. The four patients were diagnosed with 17q12 deletion syndrome with 1.47-1.76 Mb heterogeneous deletion, which led to the haploinsufficiency of HNF1B, ACACA, LHX1, PIGW, miRNA2909 and other genes. The patients had different amount of genes deletion in TBC1D3 and paralogues, which might associate with the heterogeneous clinical phenotypes.
We first reported an adulthood diabetes onset 17q12 deletion syndrome family with the largest number of patients. The heterogeneous clinical phenotypes might be related to the haploinsufficiency of TBC1D3 and its paralogues.
17q12 缺失综合征具有异质性，其原因尚不清楚。我们阐明了成年发病的 17q12 缺失综合征伴糖尿病的临床特征，并探讨了不明确的表型-基因型相关性。
我们收集了一个具有常染色体显性遗传糖尿病和肾病的家族的临床病史和实验室结果。对 HNF1B 和一组单基因糖尿病基因进行 Sanger 测序，以鉴定单基因糖尿病。进行半定量 PCR 和染色体 100K 序列分析，以分析与糖尿病相关基因的拷贝数变异。使用等位基因特异性定量 PCR 进行 TBC1D3 和同源基因的诊断。对报道的病例进行了回顾和评估，以与本研究中的患者进行比较。
通过探索基因组 DNA 中的差异变异和家庭成员的临床表现，以确定可能的表型-基因型相关性。这 4 名患者被诊断为 17q12 缺失综合征，缺失大小为 1.47-1.76Mb，导致 HNF1B、ACACA、LHX1、PIGW、miRNA2909 等基因的单倍体不足。患者在 TBC1D3 和同源基因中缺失的基因数量不同，这可能与异质性的临床表型有关。
我们首次报道了一个成年发病的 17q12 缺失综合征伴糖尿病的家系，该家系患者数量最多。异质性的临床表型可能与 TBC1D3 及其同源基因的单倍体不足有关。
