title: Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumour syndrome.
abstract: BACKGROUND
  A subset of familial isolated primary hyperparathyroidism (FIHP) is a variant of hyperparathyroidism-jaw tumour syndrome (HPT-JT). AIM/PATIENTS AND METHODS: We investigated the involvement of the HRPT2, MEN1 and CASR genes in 11 provisional FIHP families and two HPT-JT families.
  
  
  RESULTS
  Germline mutations of HRPT2 were found in two of the 11 FIHP families and one of the two HPT-JT families. One FIHP family with parathyroid carcinoma and atypical adenomas and another FIHP family with cystic parathyroid adenoma had novel frameshift mutations of 518-521del and 62-66del, respectively. In a patient with HPT-JT, a de novo germline mutation of 39delC was detected. Novel somatic HRPT2 mutations of 70-73del and 95-102del were found in two of five parathyroid tumours in a family with a 518-521del mutation. Biallelic inactivation of HRPT2 by a combination of germline and somatic mutation was confirmed in the parathyroid tumours. The finding that two families diagnosed with FIHP carried HRPT2 mutations suggests that they have occult HPT-JT. In the remaining 10 families, one family had a missense MEN1 mutation. No mutations of CASR were detected.
  
  
  CONCLUSIONS
  Our results confirm the need to test for HRPT2 in FIHP families, especially those with parathyroid carcinomas, atypical adenomas or adenomas with cystic change.
authors.affiliation: Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Mizusawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Uchino
authors.forename: Takeo
authors.initials: T
authors.lastname: Iwata
authors.forename: Masaru
authors.initials: M
authors.lastname: Tsuyuguchi
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tsunenori
authors.initials: T
authors.lastname: Mizukoshi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sakurai
authors.forename: Shinichi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Beniko
authors.forename: Hideki
authors.initials: H
authors.lastname: Tahara
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kamata
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Yashiro
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nagao
authors.forename: Hossain Md
authors.initials: HM
authors.lastname: Golam
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sano
authors.forename: Shiro
authors.initials: S
authors.lastname: Noguchi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshimoto
mesh_terms: D000236:Adenoma / Q000235:genetics; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000235:genetics*; D007573:Jaw Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008745:Methylation; D018895:Microsatellite Repeats; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics; D009154:Mutation; D010282:Parathyroid Neoplasms / Q000235:genetics; D010375:Pedigree; D011401:Promoter Regions, Genetic; D044169:Receptors, Calcium-Sensing / Q000235:genetics; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C095550:CASR protein, human; C454900:CDC73 protein, human; D044169:Receptors, Calcium-Sensing; D025521:Tumor Suppressor Proteins