title: A form of autosomal dominant spondyloepiphyseal dysplasia is caused by a glycine to alanine substitution in the COL2A1 gene.
abstract: We report a family with an unusual form of autosomal dominant spondyloepiphyseal dysplasia characterized by infantile-onset disproportionate short stature with relative shortening of the spine, thoracic kyphosis, lumbar lordosis, scoliosis and premature osteoarthritis of the joints especially of the hips. Radiological findings include mild platyspondyly, vertebral end plate irregularity, irregular femoral necks, and dysplasia of the capital femoral epiphyses with flattening and irregularity present from childhood and mild variable epiphyseal dysplasia elsewhere in the skeleton. Intrafamilial variability is observed in the degree of short stature, severity of spinal and hip involvement and the age of onset of symptoms and complications. We demonstrate that this dysplasia is due to a glycine to alanine substitution in the COL2A1 gene (p.Gly862Ala), thereby expanding the phenotypic spectrum of dysplasias associated with defects in type II collagen.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton Center for Medical Genetics, Ghent University, Belgium Department of Clinical Genetics, St Michael's Hospital Department of Orthopaedic Surgery, Bristol Royal Hospital for Children, Bristol Department of Radiology, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Gabrielle S
authors.initials: GS
authors.lastname: Sellick
authors.forename: Kristein P
authors.initials: KP
authors.lastname: Hoornaert
authors.forename: Geert R
authors.initials: GR
authors.lastname: Mortier
authors.forename: Catherine
authors.initials: C
authors.lastname: King
authors.forename: Claire L
authors.initials: CL
authors.lastname: Dolling
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Newbury-Ecob
authors.forename: Martin
authors.initials: M
authors.lastname: Gargan
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hall
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Smithson
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D001483:Base Sequence; D002648:Child; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II; D004247:DNA