title: Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott-Rallison syndrome.
abstract: Wolcott-Rallison syndrome (WRS), caused by mutation in the EIF2AK3 gene encoding the PERK enzyme, is the most common cause of permanent neonatal diabetes mellitus (PNDM) in consanguineous families and isolated populations. Besides PNDM, it also includes skeletal abnormalities, liver and renal dysfunction, and other inconsistently present features. We present two siblings, who are WRS patients, and are Albanians from Kosovo born to unrelated parents. The older sister presented with PNDM, exocrine pancreatic insufficiency, short stature, microcephaly, normocytic anemia, delay in speech development, skeletal abnormalities, primary hypothyroidism, and hypoplastic nipples. Sequencing of the EIF2AK3 gene identified a homozygous mutation R902X in exon 13. The younger brother was diagnosed with PNDM and died from hepatic failure suggesting that he has been suffering from WRS as well. Including one previously reported patient from Kosovo carrying the same homozygous mutation, there are three WRS patients from this very small, ethnically homogenous region suggesting founder effect in this population.
  
  
  CONCLUSIONS
  We postulate that thyroid hypoplasia with primary subclinical hypothyroidism already reported in two WRS patients and nipple hypoplasia could also be the phenotypic reflection of the mutation of pleiotropic EIF2AK3 gene in secretory cells.
authors.affiliation: Department of Pediatrics, University Hospital Centre Zagreb, Kišpatićeva 12, Zagreb, 10000, Croatia, anspehar@gmail.com.
authors.forename: Anita
authors.initials: A
authors.lastname: Spehar Uroić
authors.forename: Vjosa
authors.initials: V
authors.lastname: Mulliqi Kotori
authors.forename: Nataša
authors.initials: N
authors.lastname: Rojnić Putarek
authors.forename: Vesna
authors.initials: V
authors.lastname: Kušec
authors.forename: Miroslav
authors.initials: M
authors.lastname: Dumić
mesh_terms: D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004838:Epiphyses / Q000002:abnormalities*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D008297:Male; D009154:Mutation; D009558:Nipples / Q000002:abnormalities*; D010009:Osteochondrodysplasias / Q000235:genetics*; D050033:Thyroid Dysgenesis / Q000235:genetics*; D019892:eIF-2 Kinase / Q000235:genetics*
chemical_list: C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase