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Permanent neonatal diabetes caused by creation of an ectopic splice site within the INS gene.

ABSTRACT: The aim of this study was to characterize the genetic etiology in a patient who presented with permanent neonatal diabetes at 2 months of age.Regulatory elements and coding exons 2 and 3 of the INS gene were amplified and sequenced from genomic and complementary DNA samples. A novel heterozygous INS mutation within the terminal intron of the gene was identified in the proband and her affected father. This mutation introduces an ectopic splice site leading to the insertion of 29 nucleotides from the intronic sequence into the mature mRNA, which results in a longer and abnormal transcript.This study highlights the importance of routinely sequencing the exon-intron boundaries and the need to carry out additional studies to confirm the pathogenicity of any identified intronic genetic variants.

SUBMITTER: Garin I

PROVIDER: S-EPMC3250427 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Permanent neonatal diabetes caused by creation of an ectopic splice site within the INS gene.

Garin Intza I Perez de Nanclares Guiomar G Gastaldo Elena E Harries Lorna W LW Rubio-Cabezas Oscar O Castaño Luis L

PloS one 20120103 1

<h4>Background</h4>The aim of this study was to characterize the genetic etiology in a patient who presented with permanent neonatal diabetes at 2 months of age.<h4>Methodology/principal findings</h4>Regulatory elements and coding exons 2 and 3 of the INS gene were amplified and sequenced from genomic and complementary DNA samples. A novel heterozygous INS mutation within the terminal intron of the gene was identified in the proband and her affected father. This mutation introduces an ectopic sp ...[more]

PMID: 22235272

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Project description:BackgroundNeonatal diabetes mellitus (NDM) is a rare form of diabetes. We analyzed a novel insulin gene (INS) mutation of a Chinese permanent neonatal diabetes mellitus (PNDM) patient to explore the clinical and genetic characteristics and put forward some opinions on treatment and its long-term management.Case descriptionA proband was recruited who was diagnosed with permanent neonatal diabetes on his first day after birth. His clinical and follow-up data were collected for 10 years. All of the family members were given an oral glucose tolerance test. Whole exome sequencing was performed on the proband, and the genomic DNA of family members was used for verification by first-generation Sanger sequencing technology. The pathogenic variant was screened according to the American College of Medical Genetics and Genomics classification guidelines and the clinical phenotype of the patient.Diagnostic assessmentThe proband was diagnosed on the first day after birth, presenting with low birth weight, progressive hyperglycemia, and insulin deficiency. His parents and grandfathers were confirmed to have normal blood sugar levels. A novel homozygous mutation of c.1T>C in the INS gene was detected in the proband, located in the initiation codon. The heterozygous mutations were found in four family members, including his mother, father, and grandfathers. With regular insulin injections, long-term regular follow-up, close monitoring of blood glucose, balanced exercise and diet, and psychological and mutual family support, the blood glucose level was well controlled; there were no acute or chronic complications during this decade. The patient's growth and nervous system development are now no different to those of the same age.ConclusionA favorable prognosis is presented for a permanent neonatal diabetes mellitus (PNDM) patient with a novel mutation in the INS gene in China. The present findings indicate that the genetic diagnosis, early use of insulin, close monitoring of blood glucose, and psychological and mutual family support for patients with INS mutation are necessary for their favorable long-term prognosis.

Dataset Information

Permanent neonatal diabetes caused by creation of an ectopic splice site within the INS gene.

Publications

Permanent neonatal diabetes caused by creation of an ectopic splice site within the INS gene.

Similar Datasets

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