The spectrum of<i>HNF1A</i>gene mutations in Greek patients with MODY3: relative frequency and identification of seven novel germline mutations

Tatsi, Christina; Kanaka‐Gantenbein, Christina; Vazeou-Gerassimidi, Adriani; Chrysis, Dionysios; Delis, Dimitrios; Tentolouris, Nikolaοs; Dacou-Voutetakis, Catherine; Chrousos, George P.; Sertedaki, Amalia

doi:10.1111/pedi.12032

Cited by 12 publications

(11 citation statements)

References 48 publications

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“…A minimum prevalence of 68-108 cases per million persons in UK is estimated [56]. Several other studies conducted in European countries show similar frequencies of MODY with GCK MODY being the most prevalent followed by HNF4A and HNF1A MODY [53][54][55][56][57][58][59][60][61][62][63][64].…”

Section: Europementioning

confidence: 87%

Screening for monogenic diabetes in primary care

Baldacchino

Pace

Vassallo

2020

Primary Care Diabetes

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Section: Europementioning

confidence: 87%

Screening for monogenic diabetes in primary care

Baldacchino

Pace

Vassallo

2020

Primary Care Diabetes

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“…Variants in genes with multiple isoforms, such as HNF1A , cannot affect all existing transcripts. The HNF1A isoform B, for example, is the most prevalent in the adult pancreas and has 7 exons, compared with 10 present in isoform A and only 6 in the isoform C . The nonsense variant c.1558C>T/p.Gln520Ter is located in exon 8 of the reference transcript [ HNF1A (A)], a position absent in other isoforms including the most prevalent pancreatic transcript [ HNF1A (B)], probably explaining the phenotypic variability observed in our family.…”

Section: Discussionmentioning

confidence: 99%

“…and has 7 exons, compared with 10 present in isoform A and only 6 in the isoform C 43. The nonsense variant c.1558C>T/p.Gln520Ter is located in exon 8 ofthe reference transcript [HNF1A (A)], a position absent in other isoforms including the most prevalent pancreatic transcript [HNF1A (B)], probably explaining the phenotypic variability observed in our family.…”

mentioning

confidence: 99%

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

et al. 2017

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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.

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“…(36–38) The trend of increased GCK- MODY compared to HNF1A- MODY is also shown in small studies in the Czech Republic,(39) Spain,(40) and Greece. (41) Between large patient registries, centralized MODY genetic testing facilities, and smaller cohort studies, the landscape of MODY and monogenic diabetes across Europe has been well studied.…”

Section: Mody Epidemiology Studiesmentioning

confidence: 99%

Undiagnosed MODY: Time for Action

2015

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Maturity-Onset Diabetes of the Young (MODY) is a monogenic form of diabetes that accounts for at least 1% of all cases of diabetes mellitus. MODY classically presents as non-insulin requiring diabetes in lean individuals younger than 25 with evidence of autosomal dominant inheritance, but these criteria do not capture all cases and can also overlap with other diabetes types. Genetic diagnosis of MODY is important for selecting the right treatment, yet ~95% of MODY cases in the U.S. are misdiagnosed. MODY prevalence and characteristics have been well-studied in some populations, such as the UK and Norway, while other ethnicities, like African and Latino, need much more study. Emerging next-generation sequencing methods are making more widespread study and clinical diagnosis increasingly feasible. This review will cover the current epidemiological studies of MODY and barriers and opportunities for moving toward a goal of access to an appropriate diagnosis for all affected individuals.

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The spectrum ofHNF1Agene mutations in Greek patients with MODY3: relative frequency and identification of seven novel germline mutations

Cited by 12 publications

References 48 publications

Screening for monogenic diabetes in primary care

Screening for monogenic diabetes in primary care

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

Undiagnosed MODY: Time for Action

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