Hui-Xuan Wu1, Long Li1, Hong Zhang1, Jun Tang2, Mei-Biao Zhang3, Hao-Neng Tang1, Yue Guo1, Zhi-Guang Zhou1, Hou-De Zhou4. 1. 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. 2. Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. 3. Department of Endocrinology and Metabolism, The First People's Hospital of Huaihua, Huaihua, 418000, Hunan, China. 4. 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. houdezhou@csu.edu.cn.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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