A recurrent 1992delCT mutation of the type X collagen gene in a Japanese patient with Schmid metaphyseal chondrodysplasia

Abstract

SummaryWe report here a recurrent frameshift mutation within the carboxyl-terminal noncollagenous domain coding region of the type X collagen gene (COLIOA1) in a Japanese patient with Schmid metaphyseal chondrodysplasia. The mutation involves deletion of a CT dinucleotide from position 1992 (1992deiCT), and produces a frameshift which creates a premature termination codon close to the site of the deletion. The predicted length of the mutant polypeptide is 664 amino acids, which is shorter than the wild type polypeptide (680 amino acids). A 1992delCT mutation of COLIOA1 has been previously reported in one family. The independent occurrence of de novo mutation of this specific dinucleotide repeat suggests that this region is a possible mutational hot spot on COLIOA1. Key WordsSchmid metaphyseal chondrodysplasia (SMCD), mutation, type X collagen gene (COLIOA1), Japanese population, heteroduplex analysis Schmid metaphyseal chondrodysplasia (SMCD) is an autosomal dominant disorder characterized by mild dwarfism and coxa vara. Seventeen different SMCD mutations reported to date have all been located within the carboxyl (C)-terminal noncollagenous domain coding region of the type X collagen gene (COLIOA1) (Warman et al

Schmid's Type of Metaphyseal Chondrodysplasia: Diagnosis and Management

“…Collagen X is a major constituent of the pericellular matrix of hypertrophic chondrocytes within the cartilage growth plate, and the expression of collagen X during endochondral ossification is intimately linked to the onset of cartilage calcification and extracellular matrix remodeling. The absence of a functional collagen X network in mice is associated with displacement of proteoglycans, altered mineral deposition, compression of the growth plate, and hematopoietic changes.…”

Novel missense mutation resulting in the substitution of tyrosine by cysteine at codon 597 of the type X collagen gene associated with Schmid metaphyseal chondrodysplasia

“…This was based on the belief that: (1) this domain was involved in the initiation of collagen trimerization, and (2) mutant domains interfered with this trimerization (Chan et al 1995). However, of the five different mutations observed in Japanese patients to date, two were located in the N-terminal domain (Pokharel et al 1995;Matsui et al 1996;Ikegawa et al 1997). This suggested that the N-terminal domain may also play a crucial role in the formation of type X collagen (Ikegawa et al 1997).…”

Morphological evolution of polypropylene/polystyrene blends in a twin‐screw extruder

“…Apart from two exceptions, all mutations in MCDS have been identified in the NC1 domain [Warman et al, 1993; Dharmavaram et al, 1994; McIntosh et al, 1994; Wallis et al, 1994, 1996; Bonaventure et al, 1995; Chan et al, 1995, 1998; McIntosh et al, 1995; Pokharel et al, 1995; Matsui et al, 1996; Stratakis et al, 1996; Ikegawa et al, 1997; Savarirayan et al, 2000; Bateman et al, 2004]. About half of the mutations would be expected to result in truncation of the NC1 domain and the other half in amino acid substitutions.…”