title: Novel homozygous SLC29A3 mutations among two unrelated Egyptian families with spectral features of H-syndrome.
abstract: OBJECTIVE
  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 SLC29A3 mutations in two unrelated Egyptian families with affected siblings of these overlapping syndromes.
  
  
  METHODS
  Clinical, laboratory, histopathological, and radiological characteristics of individuals probably diagnosed as H and/or PHID syndrome were reported. Mutation analysis of SLC29A3 gene was performed for all members of the two Egyptian families.
  
  
  RESULTS
  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 SLC29A3 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].
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genetics Unit, Pediatrics Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al-Haggar
authors.forename: Nanees
authors.initials: N
authors.lastname: Salem
authors.forename: Yahya
authors.initials: Y
authors.lastname: Wahba
authors.forename: Nermin
authors.initials: N
authors.lastname: Ahmad
authors.forename: Laurence
authors.initials: L
authors.lastname: Jonard
authors.forename: Dina
authors.initials: D
authors.lastname: Abdel-Hady
authors.forename: Amany
authors.initials: A
authors.lastname: El-Hawary
authors.forename: Ashraf
authors.initials: A
authors.lastname: El-Sharkawy
authors.forename: Abdel-Rhman
authors.initials: AR
authors.lastname: Eid
authors.forename: Amira
authors.initials: A
authors.lastname: El-Hawary
mesh_terms: D000293:Adolescent; D002648:Child; D003286:Contracture / Q000235:genetics*; D004252:DNA Mutational Analysis; D004534:Egypt; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D015614:Histiocytosis / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D033703:Nucleoside Transport Proteins / Q000235:genetics*
chemical_list: D033703:Nucleoside Transport Proteins; C501424:SLC29A3 protein, human
keywords: Egyptian; H syndrome; SLC29A3 disorders