title: Haplotype analysis reveals founder effects of thyroglobulin gene mutations C1058R and C1977S in Japan.
abstract: BACKGROUND
  Thyroglobulin (Tg) mutations were previously believed to be rare, resulting in congenital goitrous hypothyroidism. However, an increasing number of patients with Tg mutations, who are euthyroid to mildly hypothyroid, have been identified in Japan.
  
  
  OBJECTIVE
  The purpose of this study was to investigate whether the three frequently found Tg mutations, namely C1058R, C1245R, and C1977S, were caused by a founder effect.
  
  
  RESULTS
  We found 26 different mutations within the Tg gene in 52 patients from 41 families. Thirty-five patients were homozygous for the mutations, whereas the others were compound heterozygous. The occurrence of Tg mutation within the general Japanese population is one in 67,000. Patients with the C1245R mutation were found throughout Japan, whereas those with the C1058R mutation were confined to a small village on a southern island, and those with the C1977S mutation were restricted to a city. The eight patients with the C1058R mutation and the seven patients with the C1977S mutation all showed the same combinations of 18 single-nucleotide polymorphisms in the coding region of the Tg gene, which would appear in one in 810 million and one in 37 billion, respectively, control subjects.
  
  
  CONCLUSIONS
  The frequently found mutations, C1058R and C1977S, were caused by founder effects. This result suggests that Tg mutations may provide a genetic basis for the cause of familial euthyroid goiter.
authors.affiliation: Department of Clinical Laboratory Medicine, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. a-hishi@dokkyomed.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Hishinuma
authors.forename: Shuji
authors.initials: S
authors.lastname: Fukata
authors.forename: Soroku
authors.initials: S
authors.lastname: Nishiyama
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nishi
authors.forename: Masamichi
authors.initials: M
authors.lastname: Oh-Ishi
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Murata
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Ohyama
authors.forename: Nobuo
authors.initials: N
authors.lastname: Matsuura
authors.forename: Kikuo
authors.initials: K
authors.lastname: Kasai
authors.forename: Shohei
authors.initials: S
authors.lastname: Harada
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kitanaka
authors.forename: Junta
authors.initials: J
authors.lastname: Takamatsu
authors.forename: Kohji
authors.initials: K
authors.lastname: Kiwaki
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ohye
authors.forename: Takashi
authors.initials: T
authors.lastname: Uruno
authors.forename: Chisato
authors.initials: C
authors.lastname: Tomoda
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajima
authors.forename: Kanji
authors.initials: K
authors.lastname: Kuma
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Tamio
authors.initials: T
authors.lastname: Ieiri
mesh_terms: D018703:Founder Effect; D005787:Gene Frequency; D006042:Goiter / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007037:Hypothyroidism / Q000175:diagnosis / Q000235:genetics; D007231:Infant, Newborn; D007564:Japan; D009154:Mutation / Q000235:genetics*; D015997:Neonatal Screening; D020641:Polymorphism, Single Nucleotide; D013954:Thyroglobulin / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood
chemical_list: D013972:Thyrotropin; D013954:Thyroglobulin