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Platyspondylic lethal dysplasia torrance type with a heterozygous mutation in the triple helical domain of COL2A1 in two sibs from phenotypically normal parents
Author(s) -
Okamoto Toshio,
Nagaya Ken,
Asai Hiroko,
Tsuchida Etsushi,
Nohara Fumikatsu,
Hayashi Tokitsugi,
Yamashita Akiko,
Nishimura Gen,
Azuma Hiroshi
Publication year - 2012
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35509
Subject(s) - mutation , phenotype , exon , biology , dysplasia , genetics , heterozygote advantage , point mutation , microbiology and biotechnology , gene , allele
Abstract Heterozygous COL2A1 mutations create a group of skeletal dysplasias collectively termed type II collagenopathies. Sporadic cases of type II collagenopathies are almost exclusively caused by de novo mutations. Very few cases with intrafamilial recurrence due to germinal mosaicism have been known. We report here on a family in which a severe form of skeletal dysplasia was recurrent in two sibs whose phenotype was most consistent with platyspondylic lethal skeletal dysplasia Torrance type (PLSD‐T). A COL2A1 analysis showed that the two sibs had a heterozygous mutation in the encoded triple helical region of COL2A1 , c.3545G>A (p.Gly1182Asp) in exon 50. The parents did not consent to a molecular analysis; however, the presence of the same mutation in the two sibs is proof of germinal mosaicism in one of the parents. PLSD‐T has been shown to arise from a heterozygous dominant negative COL2A1 mutation in the encoded C‐propeptide region. However, our observation suggests that the phenotype is also caused by a COL2A1 mutation in the encoded C‐terminal triple helical region. © 2012 Wiley Periodicals, Inc.