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Licensed Unlicensed Requires Authentication Published by De Gruyter August 3, 2016

Novel homozygous likely-pathogenic intronic variant in INS causing permanent neonatal diabetes in siblings

  • Rachel Courtney , Candace Gamble , Monica L. Arango , Avni Shah , Nunilo I. Rubio , Joanne Nguyen and David Rodriguez-Buritica EMAIL logo


Permanent neonatal diabetes (PNDM) is a rare genetic condition characterized by hyperglycemia, insulinopenia, and failure to thrive beginning in the first 6 months of life. Recessive mutations in INS lead to decreased production of insulin via a variety of mechanisms. We present a case of two brothers, born to consanguineous parents, with a novel homozygous intronic variant in the INS gene. Each patient presented with intrauterine growth restriction (IUGR) and significant hyperglycemia within the first 24 h of life. All the grandparents have a diagnosis of diabetes, one of them requiring insulin treatment and the parents currently deny personal histories of diabetes. Although this mutation has not previously been described, given the segregation of the mutation, absence of heterozygosity (AOH) in the genomic region encompassing the INS locus, documented insulinopenia, and high neonatal insulin requirements, we suspect that this variant is pathogenic. Possible implications for personalized treatment of the underlying molecular etiology for an individual’s diabetes are discussed.

Corresponding author: David Rodriguez-Buritica, MD, Division of Medical Genetics, Department of Pediatrics, UT Health, The University of Texas Health Science Center at Houston, McGovern Medical School, 6431 Fannin Street, MSB 3.144, Houston, TX 77030, USA, Phone: +713-500-5755, Fax: +713-383-1475


We gratefully thank the family for their participation in this study.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted article and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


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Received: 2016-1-31
Accepted: 2016-6-1
Published Online: 2016-8-3
Published in Print: 2016-9-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

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