New HNF-1α nonsense mutation causes maturity-onset diabetes of the young type 3

Nogaroto, Viviane; Svidnicki, Paulo Vinícius; Bonatto, Naieli; Milléo, Fábio Quirillo; Almeida, Mara Cristina de; Vicari, Marcelo Ricardo; Artoni, Roberto Ferreira

doi:10.1590/s1807-59322011000100029

Cited by 3 publications

(4 citation statements)

References 18 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data allow us to estimate the number of MODY cases in Brazil as approximately 140 000 to 280 000. However, until 2016, around 200 subjects of about 50 Brazilian families diagnosed with the 2 most common subtypes of MODY ( GCK and HNF1A ) have been described . Hence, MODY cases are clearly underestimated in Brazil.…”

Section: Introductionmentioning

confidence: 99%

“…However, until 2016, around 200 subjects of about 50 Brazilian families diagnosed with the 2 most common subtypes of MODY (GCK and HNF1A) have been described. [5][6][7][8][9][10][11][12][13][14][15][16][17][18] Hence, MODY cases are clearly underestimated in Brazil. Besides that, there is a great racial diversity in Brazilian people, contributing to a wide genetic background, an important difference from countries with more homogeneous population.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Clinical application of ACMG‐AMP guidelines in HNF1A and GCK variants in a cohort of MODY families

et al. 2017

View full text Add to dashboard Cite

Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. GCK -MODY and HNF1A -MODY are the prevalent subtypes. Currently, there is growing concern regarding the correct interpretation of molecular genetic findings. The American College of Medical Genetics and Genomics (ACMG) updated guidelines to interpret and classify molecular variants. This study aimed to determine the prevalence of MODY ( GCK / HNF1A ) in a large cohort of Brazilian families, to report variants related to phenotype, and to classify them according to ACMG guidelines. One hundred and nine probands were investigated, 45% with clinical suspicion of GCK -MODY and 55% with suspicion of HNF1A -MODY. Twenty-five different variants were identified in GCK gene (30 probands-61% of positivity), and 7 variants in HNF1A (10 probands-17% of positivity). Fourteen of them were novel (12- GCK /2- HNF1A ). ACMG guidelines were able to classify a large portion of variants as pathogenic (36%- GCK /86%- HNF1A ) and likely pathogenic (44%- GCK /14%- HNF1A ), with 16% (5/32) as uncertain significance. This allows us to determine the pathogenicity classification more efficiently, and also reinforces the suspected associations with the phenotype among novel variants.

show abstract

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Clinical application of ACMG‐AMP guidelines in HNF1A and GCK variants in a cohort of MODY families

et al. 2017

View full text Add to dashboard Cite

show abstract

“…GCK mutations are more commonly diagnosed in countries where glucose screening in asymptomatic people is a routine procedure (such as Germany, France, Spain and Italy), whereas HNF1A-MODY is more commonly diagnosed were routine glucose screening is seldom done (12,13). There also some reported MODY cases in Brazilian literature (14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

Maturity onset diabetes of young type 2 due to a novel de novo GKC mutation

Afonso¹,

Ferraria²,

Carvalho³

et al. 2014

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

SUMMARYMaturity Onset Diabetes of Young (MODY) is a heterogeneous group of monogenic disorders that result in β-cell dysfunction, with an estimated prevalence of 1%-2% in industrialized countries. MODY generally occurs in non-obese patients with negative autoantibodies presenting with mild to moderate hyperglycemia. The clinical features of the patients are heterogeneous, depending on the different genetic subtypes. We pretend to report a case of MODY type 2 caused by a novel de novo CGK mutation, highlighting the importance of the differential diagnosis in pediatric diabetes. A 13-year-old, healthy and non-obese girl was admitted for investigation of recurrent hyperglycemia episodes. She presented with persistent high levels of fasting blood glycemia (> 11.1 mmol/L) and had no familial history of diabetes. The blood glucose profile revealed an impaired fasting glucose of 124 mg/dL (6,9 mmol/L) with a normal oral glucose tolerance test. Fasting insulinemia was 15 mg/dL (90.1 pmol/L), HOMA-IR was 3.9 and hemoglobin A1c was 7.1%. Pancreatic autoantibodies were negative. Genetic testing identified a novel missense heterozygous mutation in exon 5 of GCK gene c.509G > T (p.Gly170Val), not present on the parents. This result established the diagnosis of MODY type 2. Clinical identification of patients with MODY remains a diagnostic challenge, especially when familial history is absent. Molecular diagnosis is very important for establishing an individualized treatment and providing a long term prognosis for each type of MODY. Arq Bras Endocrinol Metab. 2014;58(7):772-5 SUMáRioO diabetes da maturidade com início na juventude (MODY) é um grupo heterogêneo de doenças monogênicas que resultam em disfunção das células β, com uma prevalência estimada de 1-2% nos países industrializados. O MODY geralmente ocorre em pacientes não obesos, negativos para autoanticorpos e que apresentam hiperglicemia de leve a moderada. As características clínicas dos pacientes são heterogêneas e dependem do subtipo genético. Pretende-se relatar um caso de MODY tipo 2 causado por uma mutação GKC de novo não descrita anteriormente, demonstrando a importância do diagnóstico diferencial no diabetes pediátrico. Uma menina de 13 anos de idade, saudável e não obesa, foi admitida em um hospital para investigação de episódios recorrentes de hiperglicemia. Ela apresentava níveis altos e persistentes de glicemia de jejum (> 11,1 mmol/L) e não havia histórico familiar de diabetes. O perfil glicêmico sanguí-neo revelou glicose de jejum de 124 mg/dL (6,9 mmol/L), com resultados normais no teste oral de tolerância à glicose. O resultado da insulinemia de jejum foi 15 mg/dL (90,1 pmol/L), do HOMA-IR foi 3,9 e da hemoglobina A1c foi de 7,1%. Os autoanticorpos pancreáticos foram negativos. A análise genética identificou uma nova mutação heterozigota missense no éxon 5 do gene GCK c.509G > T (p.Gly170Val), não encontrada nos país. Esse resultado estabeleceu o diagnóstico de MODY tipo 2. A identificação clínica dos pacientes com MODY permanece um desafio diagnóstic...

show abstract

“…Genomic DNA was extracted from blood samples with commercial kits (Qiagen). PCR (Polymerase Chain Reaction) amplification was with oligonucleotides for the flanking regions of 10 exons of the HNF1 α gene ( Nogaroto et al , 2011 ). Following electrophoresis, the samples were purified using commercial kits (Roche), and then sequenced in an automatic ABI-PRISM 3100 sequencer (Applied Biosystems).…”

mentioning

confidence: 99%

Variants of the HNF1α gene: a molecular approach concerning diabetic patients from southern Brazil

et al. 2012

Self Cite

View full text Add to dashboard Cite

Maturity Onset Diabetes of the Young (MODY) presents monogenic inheritance and mutation factors which have already been identified in six different genes. Given the wide molecular variation present in the hepatocyte nuclear factor-1α gene (HNF1α) MODY3, the aim of this study was to amplify and sequence the coding regions of this gene in seven patients from the Campos Gerais region, Paraná State, Brazil, presenting clinical MODY3 features. Besides the synonymous variations, A15A, L17L, Q141Q, G288G and T515T, two missense mutations, I27L and A98V, were also detected. Clinical and laboratory data obtained from patients were compared with the molecular findings, including the I27L polymorphism that was revealed in some overweight/obese diabetic patients of this study, this corroborating with the literature. We found certain DNA variations that could explain the hyperglycemic phenotype of the patients.

show abstract

New HNF-1α nonsense mutation causes maturity-onset diabetes of the young type 3

Cited by 3 publications

References 18 publications

Clinical application of ACMG‐AMP guidelines in HNF1A and GCK variants in a cohort of MODY families

Clinical application of ACMG‐AMP guidelines in HNF1A and GCK variants in a cohort of MODY families

Maturity onset diabetes of young type 2 due to a novel de novo GKC mutation

Variants of the HNF1α gene: a molecular approach concerning diabetic patients from southern Brazil

Contact Info

Product

Resources

About