title: Spondyloepiphyseal dysplasia congenita caused by double heterozygous mutations in COL2A1.
abstract: Spondyloepiphyseal dysplasia congenita (SEDC) is a group of rare inherited chondrodysplasias characterized by short stature, abnormal epiphyses, and flattened vertebral bodies. SEDC is usually caused by substitution of glycine residue with another amino acid in the triple helical domains of alpha 1 chains, which consist of type II collagen (COL2A1). Herein, we describe a unique case of SEDC with mild coxa vara (SEDC-M) caused by double de novo COL2A1 mutations located on the same allele. One mutation, p.G504S, was previously described in patients with SEDC, whereas the other, p.G612A, was a novel mutation; both were located in the triple helical domain. Neither mutation was identified in the parents and appeared to be de novo. To the best of our knowledge, this is the first study involving a patient with a type II collagenopathy with two COL2A1 mutations on the same allele. The case was characterized by a more severe phenotype compared with previously reported cases involving a single p.G504S mutation, which may have been the result of the double mutation.
authors.affiliation: Department of Pediatrics, Obihiro Kyokai Hospital, Obihiro, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kawano
authors.affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Kita-ku, Sapporo, Japan.
authors.forename: Akie
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Kita-ku, Sapporo, Japan.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Morikawa
authors.affiliation: Department of Pediatrics, Obihiro Kousei Hospital, Obihiro, Japan.
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Uetake
authors.affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Kita-ku, Sapporo, Japan.
authors.forename: Katsura
authors.initials: K
authors.lastname: Ishizu
authors.affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Kita-ku, Sapporo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajima
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002675:Child, Preschool; D024043:Collagen Type II / Q000235:genetics*; D060905:Coxa Vara / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D010009:Osteochondrodysplasias / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II
keywords: COL2A1; double mutations; spondyloepiphyseal dysplasia; type II collagenopathies