Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing

Ağladıoğlu, Sebahat Yılmaz; Aycan, Zehra; Çeti̇nkaya, Semra; Baş, Veysel Nijat; Önder, Aşan; Kendırcı, Havva Nur Peltek; Doğan, Haldun; Ceylaner, Serdar

doi:10.1515/jpem-2015-0039

Cited by 33 publications

(29 citation statements)

References 33 publications

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“…In these populations, NEUROD1 mutations range from low frequencies as in Poland (0.64%; Szopa et al, ) to high frequencies as in India (7.14%; Chapla et al, ). In our study, we found a frequency of 4%, similar to that observed in Turkish (4.65%; Ağladıoğlu et al, ; Table ).…”

Section: Discussionsupporting

confidence: 90%

“…In 1999, mutations in NEUROD1 were associated to early onset type 2 diabetes mellitus (DM) in two European descendent families inherited in an autosomal dominant fashion for the first time (Malecki et al, ), being further classified as maturity‐onset diabetes of the young type 6 (MODY6; OMIM #606394) (Fajans, Bell, & Polonsky, ). Almost 20 years after the first report, only a few families in Europe (Ağladıoğlu et al, ; Gonsorčíková et al, ; Kristinsson et al, ; Szopa et al, ) and Asia (Ang et al, ; Chapla et al, ; Doddabelavangala Mruthyunjaya et al, ; Horikawa et al, ; Liu et al, ) had shown mutations in NEUROD1 as the cause of diabetes.…”

Section: Introductionmentioning

confidence: 99%

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The first case of NEUROD1‐MODY reported in Latin America

Abreu

Tarantino

Cabello

et al. 2019

Molec Gen & Gen Med

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BackgroundMODY‐NEUROD1 is a rare form of monogenic diabetes caused by mutations in Neuronal differentiation 1 (NEUROD1). Until now, only a few cases of MODY‐NEUROD1 have been reported worldwide and the real contribution of mutations in NEUROD1 in monogenic diabetes and its clinical impact remain unclear.MethodsGenomic DNA was isolated from peripheral blood lymphocytes of 25 unrelated Brazilians patients with clinical characteristics suggestive of monogenic diabetes and the screening of the entire coding region of NEUROD1 was performed by Sanger sequencing.ResultsWe identified one novel frameshift deletion (p.Phe256Leufs*2) in NEUROD1 segregating in an autosomal dominant inheritance fashion. Almost 20 years after the first report of NEUROD1‐MODY, only a few families in Europe and Asia had shown mutations in NEUROD1 as the cause of monogenic diabetes.ConclusionTo our knowledge, we described the first case of NEUROD1‐MODY in a Latin American family.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

The first case of NEUROD1‐MODY reported in Latin America

Abreu

Tarantino

Cabello

et al. 2019

Molec Gen & Gen Med

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“…In the present study, we have identified a novel heterozygous G-to-A substitution at 278 position (c.278G>A) that changes cysteine to tyrosine amino acid (p.C93Y) in exon 3 in HNF4A, which leads to MODY Type I. Flanagan et al (8) have reported a different de novo HNF4A mutation at the same position (p.C93S, c.278 G>C) leading to a diazoxide responsive hyperinsulinemic hypoglycemia that was diagnosed within the first week of life in a patient born with macrosomia (4.100 gr). Our group (9) did not detect HNF4A mutations in 42 children diagnosed with MODY, but Ağladıoğlu et al (10) analyzed 43 patients with MODY and identified two cases with the same heterozygous HNF4A mutations. One of the cases had a missense mutation (c.416C>T), which is associated with Type II diabetes mellitus in the HGMD.…”

Section: Discussionmentioning

confidence: 73%

“…Of all MODY cases, 20-50% are caused by GCK and HNF1A, approximately 10% are from a mutation of HNF4A or HNF1B (3). Studies from our country reported that GCK is the most common subtype (9)(10)(11). In the present study, we have identified a novel heterozygous G-to-A substitution at 278 position (c.278G>A) that changes cysteine to tyrosine amino acid (p.C93Y) in exon 3 in HNF4A, which leads to MODY Type I. Flanagan et al (8) have reported a different de novo HNF4A mutation at the same position (p.C93S, c.278 G>C) leading to a diazoxide responsive hyperinsulinemic hypoglycemia that was diagnosed within the first week of life in a patient born with macrosomia (4.100 gr).…”

Section: Discussionmentioning

confidence: 92%

A Novel De Novo Missense Mutation in HNF4A Resulting in Sulfonylurea-Responsive Maturity-onset Diabetes of the Young

Acar¹,

Abacı²,

Demır³

et al. 2018

jpr

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J Pediatr Res 2018;5(3):156-60 ABS TRACTMaturity-onset diabetes of the young (MODY) is a monogenic form of diabetes, with autosomal-dominant inheritance, which usually develops before 25 years of age. MODY is classically caused by a heterozygous mutation of genes known to affect insulin production or secretion. Heterozygous inactivating hepatocyte nuclear factor 4A (HNF4A) mutations, one of the rare subtypes of MODY, cause impaired insulin secretion and subsequent glucose intolerance especially in adolescence. Conversely, HNF4A mutations are also known to be associated with macrosomia and hyperinsulinemic hypoglycemia in newborns. Herein, we report a rare cause of diabetes resulting from a novel heterozygous mutation in the HNF4A gene. In conclusion, genetic testing should be considered in order to establish an accurate diagnosis and provide an opinion in determining the appropriate type of treatment.

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“…Heterozygous loss‐of‐function mutations in NEUROD1 have been reported as a very rare cause of maturity‐onset diabetes of the young (MODY) and are associated with increased risk of adult onset diabetes . Homozygous mutations in the NEUROD1 gene are extremely rare with only 2 cases of PNDM and associated neurological abnormalities due to homozygous frameshift mutations reported …”

Section: Introductionmentioning

confidence: 99%

Permanent neonatal diabetes mellitus and neurological abnormalities due to a novel homozygous missense mutation inNEUROD1

et al. 2018

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The basic helix-loop-helix (bHLH) transcription factor, neuronal differentiation 1 (NEUROD1) (also known as BETA2) is involved in the development of neural elements and endocrine pancreas. Less than 10 reports of adult-onset non-insulin-dependent diabetes mellitus (NIDDM) due to heterozygous NEUROD1 mutations and 2 cases with permanent neonatal diabetes mellitus (PNDM) and neurological abnormalities due to homozygous NEUROD1 mutations have been published. A 13 year-old female was referred to endocrine department due to hyperglycemia. She was on insulin therapy following a diagnosis of neonatal diabetes mellitus (NDM) at the age of 9-weeks but missed regular follow-up. Parents are second cousin. There was a significant family history of adult onset NIDDM including patient's father. Auxological measurements were within normal ranges. On laboratory examination blood glucose was 33.2 mmol/L with undetectable c-peptide and glycosylated hemoglobin level of 8.9% (73.8 mmol/mol). She had developed difficulty in walking at the age of 4 years which had worsened over time. On further evaluation, a diagnosis of visual impairment, mental retardation, ataxic gait, retinitis pigmentosa and sensory-neural deafness were considered. Cranial magnetic resonance imaging revealed cerebellar hypoplasia. Molecular genetic analysis using targeted next generation sequencing detected a novel homozygous missense mutation, p.Ile150Asn(c.449T>A), in NEUROD1. Both parents and 2 unaffected siblings were heterozygous for the mutation. We report the third case of PNDM with neurological abnormalities caused by homozygous NEUROD1 mutation, the first caused by a missense mutation. Heterozygous carriers of the p.Ile150Asn mutation were either unaffected or diagnosed with diabetes in adulthood. It is currently unclear whether the NEUROD1 heterozygous mutation has contributed to diabetes development in these individuals.

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Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing

Cited by 33 publications

References 33 publications

The first case of NEUROD1‐MODY reported in Latin America

The first case of NEUROD1‐MODY reported in Latin America

A Novel De Novo Missense Mutation in HNF4A Resulting in Sulfonylurea-Responsive Maturity-onset Diabetes of the Young

Permanent neonatal diabetes mellitus and neurological abnormalities due to a novel homozygous missense mutation inNEUROD1

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