title: HNF1alpha mutations are present in half of clinically defined MODY patients in South-Brazilian individuals.
abstract: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset, and pancreatic beta cell dysfunction. Heterozygous mutations in at least seven genes can cause MODY. In the present study we investigated the relative prevalence of GCK (glucokinase) and HNF1alpha (hepatocyte nuclear factor 1alpha) mutations, the more frequent causes of MODY, in 13 South-Brazilian families with multiple cases of diabetes consistent with MODY. Heterozygous variants in GCK and HNF1alpha genes were observed respectively in one (7.7%), and six (46.2%) families. The six HNF1alpha variants are likely to cause diabetes in the families where they were observed. However, we could not ascertain whether the GCK Gly117Ser variant found in one family is a causal mutation. In conclusion, we have confirmed in a South-Brazilian population that HNF1alpha mutations are a common cause of monogenic diabetes in adults selected with strict clinical diagnostic criteria.
authors.affiliation: Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Jorge de Faria
authors.initials: Jde F
authors.lastname: Maraschin
authors.forename: Caroline
authors.initials: C
authors.lastname: Kannengiesser
authors.forename: Nádia
authors.initials: N
authors.lastname: Murussi
authors.forename: Nicole
authors.initials: N
authors.lastname: Campagnolo
authors.forename: Luís Henrique
authors.initials: LH
authors.lastname: Canani
authors.forename: Jorge Luiz
authors.initials: JL
authors.lastname: Gross
authors.forename: Gilberto
authors.initials: G
authors.lastname: Velho
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
authors.forename: Sandra Pinho
authors.initials: SP
authors.lastname: Silveiro
mesh_terms: D000328:Adult; D001938:Brazil; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005941:Glucokinase / Q000235:genetics*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D015995:Prevalence; D055815:Young Adult
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; D005941:Glucokinase