title: A novel p. Gly630Ser mutation of COL2A1 in a Chinese family with presentations of Legg-Calvé-Perthes disease or avascular necrosis of the femoral head.
abstract: OBJECTIVE
  Mutations in the type II collagen gene are associated with certain human disorders, collectively termed type II collagenopathies. They include Legg-Calvé-Perthes disease (LCPD) and avascular necrosis of the femoral head (ANFH). These two diseases are skeletal dysplasias, inherited in an autosomal dominant fashion, characterized by groin pain, dislocation of the hip and diminished joint mobility. Coxa vara and elevation of the greater trochanter of the femur comprise the typical phenotype of LCPD, but do not occur in ANFH. Lack of synthesis of type II collagen and structural defects are responsible for the major clinical outcomes, because collagen is the essential matrix protein of all connective tissues. Type II collagen, encoded by the COL2A1 gene, contains N- and C- terminal regions that are cleaved after secretion into the extracellular matrix, and the core area is composed of a triple helical (Gly-X-Y) domain. If the Gly in this specific region is replaced by other amino acids, the structure of type II collagen will be destroyed.
  
  
  METHODS
  Forty-five members of a four-generation family were recruited and investigated. Diagnosis was made by independent orthopedic surgeons and radiologists. A mutation of the COL2A1 gene was detected.
  
  
  RESULTS
  In our research, we identify a heterozygous mutation (c.1888 G>A, p. Gly630Ser) in exon 29 of COL2A1 in the Gly-X-Y domain, in a Chinese family affected by LCPD and ANFH. Our findings provide significant clues to the phenotype-genotype relationships in these syndromes and may be helpful in clinical diagnosis. Furthermore, these results should assist further studies of the mechanisms underlying collagen diseases.
  
  
  CONCLUSIONS
  Our data add new variants to the repertoire of COL2A1 mutation resulting in related collagenopathies.
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cao
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Qiu-Yue
authors.initials: QY
authors.lastname: Wu
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Li
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Tian-Fu
authors.initials: TF
authors.lastname: Li
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Cui
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Ying-Xia
authors.initials: YX
authors.lastname: Cui
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Yin
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Xia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D024043:Collagen Type II / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005271:Femur Head Necrosis / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D007873:Legg-Calve-Perthes Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011859:Radiography; D051381:Rats
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II