Novel homozygous SLC29A3 mutations among two unrelated Egyptian families with spectral features of H‐syndrome. Issue 4 (4th June 2014)

• Record Type: Journal Article
• Authors: Al‐Haggar, Mohammad; Salem, Nanees; Wahba, Yahya; Ahmad, Nermin; Jonard, Laurence; Abdel‐Hady, Dina; El‐Hawary, Amany; El‐Sharkawy, Ashraf; Eid, Abdel‐Rhman; El‐Hawary, Amira
• Is Part Of: Pediatric diabetes. Volume 16:Issue 4(2015:Jul.)
• Page Start: 305
• Page End: 316
• Publication Date: 2014-06-04
• Subjects: Diabetes in children -- Periodicals; 616.462
• DOI: 10.1111/pedi.12160
• Languages: English
• ISSNs: 1399-543X

Abstract

<abstract abstract-type="main" id="pedi12160-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pedi12160-sec-0001" sec-type="section"> <title>Objectives</title> <p id="pedi12160-para-0001">H syndrome and pigmented hypertrichosis with insulin‐dependent diabetes mellitus (PHID) had been described as two autosomal recessive disorders. We aim to screen for pathogenic <italic>SLC29A3</italic> mutations in two unrelated Egyptian families with affected siblings of these overlapping syndromes.</p> </sec> <sec id="pedi12160-sec-0002" sec-type="section"> <title>Methods</title> <p id="pedi12160-para-0002">Clinical, laboratory, histopathological, and radiological characteristics of individuals probably diagnosed as H and/or PHID syndrome were reported. Mutation analysis of <italic>SLC29A3</italic> gene was performed for all members of the two Egyptian families.</p> </sec> <sec id="pedi12160-sec-0003" sec-type="section"> <title>Results</title> <p id="pedi12160-para-0003">All affected individuals were females; proband of family‐I (A1961) displayed overlapping features of H syndrome and PHID, while her younger brother (A1962) was asymptomatic. A1961 presented with previously undescribed features; absent pectoralis major muscle and a supracondylar bony spur in left humerus. In family‐II, probands (A1965 and A1966) had clinical features consistent with classical H syndrome with unique early onset of cutaneous phenomena at birth. Mutation analysis of <italic>SLC29A3</italic> revealed homozygous mutation previously reported in literature c.1279G>A [p.G427S] in A1961 and unexpectedly in the asymptomatic A1962 of family‐I. Probands of family‐II were homozygous for a novel mutation c.401G>A [p.R134H], in the same codon that was published in an Indian boy [p.R134C].</p> </sec> <sec id="pedi12160-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="pedi12160-para-0004">We emphasize the inter‐ and intra‐familial genetic heterogeneity among Egyptian patients with overlapping features of SLC29A3 disorders. This suggests the presence of other factors like regulatory genes or epigenetic factors that may explain variable disease manifestations and severity.</p> </sec> </abstract>