MODY 2: Mutation identification and molecular ancestry in a Brazilian family |
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Authors: | Adolfo J. Mota,Simone Brü ggemann,Fabrí cio F. Costa |
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Affiliation: | 1. Departamento de Biociências e Diagnóstico Oral, Faculdade de Odontologia de São José dos Campos, Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), São José dos Campos, SP, Brazil;2. Prefeitura Municipal de Sao Jose dos Campos (PMSJC), Sao Jose dos Campos, SP, Brazil;3. Cancer Biology and Epigenomics Program, Children''s Hospital of Chicago Research Center and Department of Pediatrics, Northwestern University''s Feinberg School of Medicine, Chicago, IL 60614, USA;4. Datagenno Interactive Research Ltda, Rua Gastão Machado 66, Edifício CME, Salas 503/504, Campos dos Goytacazes, Rio de Janeiro, RJ 28035-120, Brazil |
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Abstract: | Maturity Onset Diabetes of the Young (MODY) is a heterogeneous group of genetic diseases characterized by a primary defect in insulin secretion and hyperglycemia, non-ketotic disease, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of auto-antibodies. It accounts for 2–5% of all cases of non-type 1 diabetes. MODY subtype 2 is caused by mutations in the glucokinase (GCK) gene. In this study, we sequenced the GCK gene of two volunteers with clinical diagnosis for MODY2 and we were able to identify four mutations including one for a premature stop codon (c.76C>T). Based on these results, we have developed a specific PCR-RFLP assay to detect this mutation and tested 122 related volunteers from the same family. This mutation in the GCK gene was detected in 21 additional subjects who also had the clinical features of this genetic disease. In conclusion, we identified new GCK gene mutations in a Brazilian family of Italian descendance, with one due to a premature stop codon located in the second exon of the gene. We also developed a specific assay that is fast, cheap and reliable to detect this mutation. Finally, we built a molecular ancestry model based on our results for the migration of individuals carrying this genetic mutation from Northern Italy to Brazil. |
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Keywords: | MODY, Maturity Onset Diabetes of the Young GCK, glucokinase PCR, Polymerase Chain Reaction RFLP, Restriction Fragment Length Polymorphism OMIM, Online Mendelian Inheritance in Men HNF1A, hepatocyte nuclear factor-1-alpha PDX1, homeobox protein-1 NIDDM, non-insulin-dependent diabetes mellitus IC, informed consent ICAs, C-peptide and islet cell antibodies IFCC-HbA1c, glycated hemoglobin FBG, fasting blood glucose |
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