title: A novel mutation in COL2A1 leading to spondyloepiphyseal dysplasia congenita in a three-generation family.
abstract: OBJECTIVE
  To investigate the genotype of COL2A1 in a three-generation spondyloepiphyseal dysplasia congenita (SEDC) family.
  
  
  METHODS
  Five affected individuals from a Chinese SEDC family were enrolled in the study. All patients underwent thorough physical and radiographic examinations. DNA samples of the affected patients and the healthy controls were collected with the informed consent obtained from each participant. Two short tandem repeat polymorphic markers flanking COL2A1 gene region were detected to determine the haplotype of each patient. Subsequently, sequence analysis was performed in COL2A1 gene to identify potential genetic mutation.
  
  
  RESULTS
  Haplotype analysis showed that the same disease-associated haplotype was segregated through the whole pedigree. A maximum LOD score of 1.5 was obtained with D12S85 and D12S368. DNA sequence analysis revealed a c.1636 G/A transition in exon 25 of the COL2A1 gene, which converted the codon GGT for glycine at position 546 to AGT, a codon for serine. The patients were all heterozygous for the mutation G546S, which was absent in either of the unaffected family members or of the normal individuals.
  
  
  CONCLUSIONS
  This is the first familial report of G546S mutation in the COL2A1 gene that results in SEDC. Although great achievements have been made in the recognition of the mutation spectrum, more intensive studies are warranted to further identify correlations between genotype and phenotype.
authors.affiliation: Department of Spine Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Xu
authors.forename: Xusheng
authors.initials: X
authors.lastname: Qiu
authors.forename: Zezhang
authors.initials: Z
authors.lastname: Zhu
authors.forename: Long
authors.initials: L
authors.lastname: Yi
authors.forename: Yong
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002648:Child; D002681:China; D024043:Collagen Type II / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010009:Osteochondrodysplasias / Q000151:congenital* / Q000235:genetics; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II
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