title: Type II collagen gene variants and inherited osteonecrosis of the femoral head.
abstract: BACKGROUND
  Avascular necrosis of the femoral head (ANFH) causes disability that often requires surgical intervention. Most cases of ANFH are sporadic, but we identified three families in which there was autosomal dominant inheritance of the disease and mapped the chromosomal position of the gene to 12q13.
  
  
  METHODS
  We carried out haplotype analysis in the families, selected candidate genes from the critical interval for ANFH on 12q13, and sequenced the promoter and exonic regions of the type II collagen gene (COL2A1) from persons with inherited and sporadic forms of ANFH.
  
  
  RESULTS
  We identified a G-->A transition in exon 50 of COL2A1 in affected members of a four-generation family with ANFH. This transition predicts the replacement of glycine with serine at codon 1170 in a GXY repeat of type II collagen. Another pedigree was shown to harbor the same transition, but the mutant allele occurred on a different haplotype background. In a third family, a G-->A transition in exon 33 of the gene, causing a glycine-to-serine change at codon 717, was detected. No mutation was found in the COL2A1 coding region in sporadic cases of ANFH.
  
  
  CONCLUSIONS
  All the patients with familial ANFH whom we studied carried COL2A1 mutations. In families with ANFH, haplotype and sequence analysis of the COL2A1 gene can be used to identify carriers of the mutant allele before the onset of clinical symptoms, allowing the initiation of measures that may delay progression of the disease.
authors.affiliation: Institute of Genetics and Genome Research Center, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Liu
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chen
authors.forename: Yung-Feng
authors.initials: YF
authors.lastname: Lin
authors.forename: Ruei-Cheng
authors.initials: RC
authors.lastname: Yang
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Ling-Hui
authors.initials: LH
authors.lastname: Li
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chang
authors.forename: Yuh-Shan
authors.initials: YS
authors.lastname: Jou
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Lin
authors.forename: Jih-Shyun
authors.initials: JS
authors.lastname: Su
authors.forename: Shiu-Feng
authors.initials: SF
authors.lastname: Huang
authors.forename: Kwang-Jen
authors.initials: KJ
authors.lastname: Hsiao
authors.forename: Cathy S J
authors.initials: CS
authors.lastname: Fann
authors.forename: Hun-Way
authors.initials: HW
authors.lastname: Hwang
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Tsai
mesh_terms: D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D024043:Collagen Type II / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005271:Femur Head Necrosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D011859:Radiography; D017422:Sequence Analysis, DNA
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II