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Accurate diagnosis and heterogeneity analysis of a 17q12 deletion syndrome family with adulthood diabetes onset and complex clinical phenotypes
- Source :
- Endocrine. 73(1)
- Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Adult
Sequence analysis
Endocrinology, Diabetes and Metabolism
030209 endocrinology & metabolism
Biology
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Endocrinology
Diabetes mellitus
Proto-Oncogene Proteins
medicine
Humans
Allele
Hepatocyte Nuclear Factor 1-beta
Genetics
Sanger sequencing
GTPase-Activating Proteins
Chromosome
Syndrome
medicine.disease
HNF1B
Phenotype
Diabetes Mellitus, Type 2
030220 oncology & carcinogenesis
symbols
Chromosome Deletion
Haploinsufficiency
Subjects
Details
- ISSN :
- 15590100
- Volume :
- 73
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Endocrine
- Accession number :
- edsair.doi.dedup.....0992e3f7db7604c459edc41f25a82c17