Research

MODY-like diabetes associated with an apparently balanced translocation: possible involvement of MPP7 gene and cell polarity in the pathogenesis of diabetes

Elizabeth J Bhoj¹ , Stefano Romeo^1,2 , Marco G Baroni² , Guy Bartov³ , Roger A Schultz^3,5 and Andrew R Zinn^1,4

¹  McDermott Center for Human Growth and Development, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA

²  Department of Medical Sciences, Endocrinology, University of Cagliari, Cagliari, Italy

³  Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA

⁴  Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA

⁵  Signature Genomic Laboratories, LLC, Spokane, WA, USA

author email corresponding author email

Molecular Cytogenetics 2009, 2:5doi:10.1186/1755-8166-2-5

Published:	13 February 2009

Abstract

Background

Characterization of disease-associated balanced translocations has led to the discovery of genes responsible for many disorders, including syndromes that include various forms of diabetes mellitus. We studied a man with unexplained maturity onset diabetes of the young (MODY)-like diabetes and an apparently balanced translocation [46,XY,t(7;10)(q22;p12)] and sought to identify a novel diabetes locus by characterizing the translocation breakpoints.

Results

Mutations in coding exons and splice sites of known MODY genes were first ruled out by PCR amplification and DNA sequencing. Fluorescent in situ hybridization (FISH) studies demonstrated that the translocation did not disrupt two known diabetes-related genes on 10p12. The translocation breakpoints were further mapped to high resolution using FISH and somatic cell hybrids and the junctions PCR-amplified and sequenced. The translocation did not disrupt any annotated transcription unit. However, the chromosome 10 breakpoint was 220 kilobases 5' to the Membrane Protein, Palmitoylated 7 (MPP7) gene, which encodes a protein required for proper cell polarity. This biological function is shared by HNF4A, a known MODY gene. Databases show MPP7 is highly expressed in mouse pancreas and is expressed in human islets. The translocation did not appear to alter lymphoblastoid expression of MPP7 or other genes near the breakpoints.

Conclusion

The balanced translocation and MODY-like diabetes in the proband could be coincidental. Alternatively, the translocation may cause islet cell dysfunction by altering MPP7 expression in a subtle or tissue-specific fashion. The potential roles of MPP7 mutations in diabetes and perturbed islet cell polarity in insulin secretion warrant further study.