Platyspondylic lethal dysplasia torrance type with a heterozygous mutation in the triple helical domain of COL2A1 in two sibs from phenotypically normal parents.
著者
岡本, 年男
(Okamoto, Toshio)
Nagaya, Ken
(Nagaya, Ken)
Asai, Hiroko
(Asai, Hiroko)
Tsuchida, Etsushi
(Tsuchida, Etsushi)
Nohara, Fumikatsu
(Nohara, Fumikatsu)
Hayashi, Tokitsugi
(Hayashi, Tokitsugi)
Yamashita, Akiko
(Yamashita, Akiko)
Nishimura, Gen
(Nishimura, Gen)
Azuma, Hiroshi
(Azuma, Hiroshi)
上位タイトル
American journal of medical genetics. Part A
Vol.158A,
No.8
(2012.
8)
,p.1953-
1956
識別番号
ISSN
1552-4825
DOI
10.1002/ajmg.a.35509
その他
PMID:22711552
抄録
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 triple helical region of COL2A1, c.3545G>A (p.G1182A) 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 believed to arise from a heterozygous dominant negative mutation in the C-propeptide region of COL2A1. However, our observation suggests that the phenotype is also caused by a mutation in the C-terminal triple helical region of COL2A1.
