title: HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer.
abstract: The genetic basis of nonsyndromic familial nonmedullary thyroid cancer (FNMTC) is poorly understood. A recent study identified HABP2 as a tumor suppressor gene and identified a germline variant (G534E) in an extended FNMTC kindred. The relevance of this to other FNMTC kindreds is uncertain.
  
  
  
  Sanger sequencing was performed on peripheral blood DNA from probands from 37 Australian FNMTC kindreds to detect the G534E variant. Whole exome data from 59 participants from 20 kindreds were examined for mutations in HABP2 and the thyroid cancer susceptibility genes SRGAP1, NKX2-1, SRRM2 and FOXE1. The population prevalence of the G534E variant in HABP2 was examined in two independent cohorts.
  
  
  
  Heterozygosity for the G534E variant in HABP2 was found in 1 of 37 probands (2.7 %), but did not cosegregate with disease in this kindred, being absent in the proband's affected sister. From whole exome data, pathogenic mutations were not identified in HABP2, SRGAP1, NKX2-1, SRRM2 or FOXE1. Heterozygosity for the G534E variant in HABP2 was present in 7.6 % of Busselton Health Study participants (N = 4634, unknown disease status) and 9.3 % of TwinsUK participants (N = 1195, no history of thyroid cancer).
  
  
  
  The G534E variant in HABP2 does not account for the familial nature of NMTC in Australian kindreds, and is common in the general population. Further research is required to elucidate the genetic basis of nonsyndromic FNMTC.
authors.affiliation: Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.|School of Medicine & Pharmacology, The University of Western Australia, Crawley, WA, 6009, Australia.
authors.forename: Alexia L
authors.initials: AL
authors.lastname: Weeks
authors.affiliation: Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.|School of Medicine & Pharmacology, The University of Western Australia, Crawley, WA, 6009, Australia.|Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Wilson
authors.affiliation: Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
authors.forename: Lynley
authors.initials: L
authors.lastname: Ward
authors.affiliation: Genetic Services of Western Australia, King Edward Memorial Hospital, Subiaco, WA, 6008, Australia.|School of Paediatrics and Child Health, The University of Western Australia, Crawley, WA, 6009, Australia.
authors.forename: Jack
authors.initials: J
authors.lastname: Goldblatt
authors.affiliation: Pathwest Laboratory Medicine WA, Nedlands, WA, 6009, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA, 6009, Australia.
authors.forename: Jennie
authors.initials: J
authors.lastname: Hui
authors.affiliation: Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia. john.walsh@health.wa.gov.au.|School of Medicine & Pharmacology, The University of Western Australia, Crawley, WA, 6009, Australia. john.walsh@health.wa.gov.au.
authors.forename: John P
authors.initials: JP
authors.lastname: Walsh
mesh_terms: D000328:Adult; D001315:Australia; D002277:Carcinoma / Q000235:genetics*; D002291:Carcinoma, Papillary; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D017422:Sequence Analysis, DNA / Q000379:methods*; D012697:Serine Endopeptidases / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C433550:HABP2 protein, human; D012697:Serine Endopeptidases
keywords: HABP2; Oncogenes; Papillary thyroid cancer; Thyroid carcinoma