title: Kallmann syndrome: somatic and germline mutations of the fibroblast growth factor receptor 1 gene in a mother and the son.
abstract: BACKGROUND
  Although Kallmann syndrome (KS) caused by heterozygous loss of function mutations of the fibroblast growth factor receptor 1 gene (FGFR1) is occasionally associated with characteristic features, such as dental agenesis and cleft palate, FGFR1 mutations remain unidentified in several KS patients with such characteristic features.
  
  
  METHODS
  We examined a 14-yr-old Japanese boy with hypogonadotropic hypogonadism, olfactory dysfunction, and dental agenesis and his fertile mother with olfactory dysfunction and dental agenesis. Direct sequencing was performed for FGFR1 using leukocyte genomic DNA from the proband and leukocyte and nail genomic DNA from the mother. To examine a possible somatic mutation, a specific forward primer was designed to introduce a BstXI site into the normal allele only, and nested PCR amplification, followed by BstXI digestion, was carried out three times with different reverse primers.
  
  
  RESULTS
  After standard PCR amplifications, a heterozygous 2-bp deletion at exon 10 (1317_1318delTG), which is predicted to cause a frameshift at the 439th codon for serine and resultant termination at the 461st codon (S439fsX461), was identified in the proband, but was not found in the mother. After selective amplification of the mutant allele, this deletion was detected in nail DNA, but not in leukocyte DNA, from the mother.
  
  
  CONCLUSIONS
  The results suggest that the 2-bp deletion took place as a somatic mutation in the mother and was transmitted to the boy because of germline mosaicism. Such a somatic mutation occurs in some apparently FGFR1 mutation-negative KS patients with dental agenesis.
authors.affiliation: Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sato
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohyama
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
authors.forename: Michiyo
authors.initials: M
authors.lastname: Okada
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D004247:DNA / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D017436:Kallmann Syndrome / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000502:physiology; D012313:RNA; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation / Q000235:genetics
chemical_list: C034477:RNA primers; D012313:RNA; D004247:DNA; D051496:Receptor, Fibroblast Growth Factor, Type 1