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Diabetes Metab. 2013 May;39(3):281-5. doi: 10.1016/j.diabet.2013.03.007. Epub 2013 Apr 23.

SLC29A3 mutation in a patient with syndromic diabetes with features of pigmented hypertrichotic dermatosis with insulin-dependent diabetes, H syndrome and Faisalabad histiocytosis.

Author information

1
Inserm UMR-S958, Medical Faculty Paris 7, site Villemin, Paris, France.

Abstract

AIMS:

Atypical forms of diabetes may be caused by monogenic mutations in key genes controlling beta-cell development, survival and function. This report describes an insulin-dependent diabetes patient with a syndromic presentation in whom a homozygous SLC29A3 mutation was identified.

METHODS:

SLC29A3 was selected as the candidate gene based on the patient's clinical manifestations, and all exons and flanking regions in the patient's genomic DNA were sequenced.

RESULTS:

A homozygous splice mutation (c.300+1G>C) resulting in a frameshift and truncated protein (p.N101LfsX34) was identified. The patient had insulin-dependent diabetes, congenital deafness, short stature, hyperpigmented patches on the skin, dysmorphic features, cardiomegaly, arthrogryposis, hepatosplenomegaly, anaemia with erythroblastopenia, and an inflammatory syndrome with fever and arthritis; she also presented with a fibrotic mediastinal mass. These clinical features overlapped with pigmented hypertrichosis with insulin-dependent diabetes (PHID), H syndrome, Faisalabad histiocytosis and sinus histiocytosis with massive lymphadenopathy (SHML), all of which are also caused by SLC29A3 mutations.

CONCLUSION:

This is the most severe case reported of SLC29A3 mutations with cumulative features of all these syndromes. This extreme severity coincides with the most N-terminal location of the truncation mutation, thereby affecting all alternative transcripts of the gene. This case report extends the clinical variability of homozygous SLC29A3 mutations that result in a spectrum of multisystemic manifestations.

PMID:
23623699
DOI:
10.1016/j.diabet.2013.03.007
[Indexed for MEDLINE]

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