Case Report: Neonatal Diabetes Mellitus Caused by a Novel GLIS3 Mutation in Twins

London, Shira; Franco, Elisa De; Elias-Assad, Ghadir; Barhoum, Marie Noufi; Felszer, Clari; Paniakov, Marina; Weiner, Scott A; Tenenbaum‐Rakover, Yardena

doi:10.3389/fendo.2021.673755

Cited by 10 publications

(20 citation statements)

References 30 publications

(58 reference statements)

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“…Previous studies have reported that recessive mutations in GLIS3 gene inherited from consanguineous parents are associated with syndromic permanent neonatal diabetes with congenital hypothyroidism. 3 The cases described so far were homozygous for the GLIS3 mutation, while the parents or healthy sibling were heterozygous carriers for the mutation. 1 For this reason, one functional allele of the GLIS3 gene seems to be sufficient with no negative phenotype effects.…”

Section: Discussionmentioning

confidence: 98%

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Case report: Neonatal diabetes mellitus with congenital hypothyroidism as a result of biallelic heterozygous mutations in GLIS3 gene

Perdas

Antosik

Hrytsiuk³

et al. 2022

Pediatric Diabetes

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Neonatal diabetes mellitus with congenital hypothyroidism (NDH) syndrome (MIM# 610199) is a rare disease caused by autosomal recessive mutations in the GLIS3 gene. GLIS3 is an important transcription factor that might acts as both a repressor and activator of transcription. To date, 22 cases of NDH syndrome from 16 families and 11 countries have been described. Herein, we report a child who developed diabetes during the first week of age. Additionally, she suffered from congenital hypothyroidism, cardiac abnormalities, and polycystic kidney disease. Genetic analysis revealed that patient is a carrier of two novel heterozygous mutations, p.Pro444fsdelG (c.1330delC) and p.His647Arg (c.1940A > G) in the GLIS3 gene. Each was inherited from clinically healthy father and mother, respectively. Bioinformatic tools (SIFT, PolyPhen2, PROVEAN and SWISS‐MODEL) declared that the p.His647Arg (c.1940A > G) variant has strong detrimental effect and disturbs Kruppel‐like zinc finger domain. All but one so far described cases of NDH syndrome have been caused by homozygous of GLIS3, making the described case the second case of pathogenic, compound heterozygosity of GLIS3 worldwide posing substantial clinical novelty and detailing an interesting interplay between the observed variants and GLIS3 expression, which seems to be autoregulated. Hence, the damaging missense mutation may further reduce the expression of any remaining functional alleles. This case report expands our understanding of the clinical phenotype, treatment approaches, and outcome of infants with GLIS3 mutations and indicates the need for further research to deepen our understanding of the role of GLIS3.

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Section: Discussionmentioning

confidence: 98%

“…To date, 22 cases of NDH syndrome from 16 families and 11 countries have been described. In 21 out of 22 cases were homozygous mutations 3 . One case was compound heterozygote of exons 1–11 deletion and a missense mutation in exon 5 (p.Arg589Trp) 4 …”

Section: Introductionmentioning

confidence: 99%

Case report: Neonatal diabetes mellitus with congenital hypothyroidism as a result of biallelic heterozygous mutations in GLIS3 gene

Perdas

Antosik

Hrytsiuk³

et al. 2022

Pediatric Diabetes

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“…Senée and colleagues in 2006 described, for the first time, a new syndrome in an infant diagnosed with NDM and CH associated with GLIS3 gene mutation [11]. So far, 22 cases have been reported in the literature, and they all exhibit phenotypic variation [11,12].…”

Section: Discussionmentioning

confidence: 99%

“…GLIS3 gene mutation predominantly presents with NDM and CH. Other systems commonly involved with this mutation are the eyes (CG), kidneys (renal cysts), and liver (hepatomegaly, hepatitis, hepatic fibrosis, cirrhosis, and cholestasis) [12]. Some less frequently associated features include dysmorphism, exocrine pancreatic insufficiency, osteopenia, sensorineural deafness, skeletal anomalies, choanal atresia, patent ductus arteriosus, atrial septal defect, and psychomotor delays [2].…”

Section: Discussionmentioning

confidence: 99%

A Neonate With Diabetes Mellitus, Congenital Hypothyroidism, and Congenital Glaucoma

Boddu¹,

Velumula²,

Sharif³

et al. 2022

Cureus

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Neonatal diabetes mellitus (NDM) is a rare condition with more than 20 monogenic genes associated with it. GLIS3 gene-encoded GLI similar protein 3, as a transcription factor, is involved in the development of the pancreas, liver, kidneys, eye, and thyroid. We report a preterm female neonate with coarse facial features and hyperglycemia, later diagnosed with neonatal diabetes mellitus, congenital hypothyroidism (CH), congenital glaucoma (CG), and renal cysts, secondary to GLIS3 gene mutation. It is a rare genetic disorder involving multiple organ systems with progressive development of symptoms requiring long-term surveillance and management.

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“…Recently, novel mutations within the coding region of GLIS3 gene have been identified. One such novel homozygous mutation created a premature stop codon within the C-terminus of GLIS3 (c.2392C>T; p.Gln798Ter) and caused a syndrome characterized by neonatal diabetes, congenital hypothyroidism, congenital glaucoma, and cystic kidney disease [ 97 ]. The premature stop codon lies within the known transactivation of the protein (see Figure 1 B), thus confirming the functional conservation of the domain from mice [ 98 ].…”

Section: Newly Identified Human Mutations Within Glis3mentioning

confidence: 99%

GLIS3: A Critical Transcription Factor in Islet β-Cell Generation

Scoville

Jetten

2021

Cells

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Understanding of pancreatic islet biology has greatly increased over the past few decades based in part on an increased understanding of the transcription factors that guide this process. One such transcription factor that has been increasingly tied to both β-cell development and the development of diabetes in humans is GLIS3. Genetic deletion of GLIS3 in mice and humans induces neonatal diabetes, while single nucleotide polymorphisms (SNPs) in GLIS3 have been associated with both Type 1 and Type 2 diabetes. As a significant progress has been made in understanding some of GLIS3’s roles in pancreas development and diabetes, we sought to compare current knowledge on GLIS3 within the pancreas to that of other islet enriched transcription factors. While GLIS3 appears to regulate similar genes and pathways to other transcription factors, its unique roles in β-cell development and maturation make it a key target for future studies and therapy.

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Case Report: Neonatal Diabetes Mellitus Caused by a Novel GLIS3 Mutation in Twins

Cited by 10 publications

References 30 publications

Case report: Neonatal diabetes mellitus with congenital hypothyroidism as a result of biallelic heterozygous mutations in GLIS3 gene

Case report: Neonatal diabetes mellitus with congenital hypothyroidism as a result of biallelic heterozygous mutations in GLIS3 gene

A Neonate With Diabetes Mellitus, Congenital Hypothyroidism, and Congenital Glaucoma

GLIS3: A Critical Transcription Factor in Islet β-Cell Generation

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