Double heterozygosity for pseudoachondroplasia and spondyloepiphyseal dysplasia congenita
Double heterozygosity for pseudoachondroplasia and spondyloepiphyseal dysplasia congenita
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DOI：
10.1002/ajmg.10062
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发表时间：
2001-11-22
期刊：
影响因子：
--
通讯作者：
Cohn, DH
中科院分区：
文献类型：
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作者：
Unger, S;Korkko, J;Cohn, DH
假性软骨发育不良(PSACH)和先天性脊柱骨骺发育不良(SEDC)是由编码软骨细胞外基质结构成分的基因突变引起的常染色体显性短肢矮小形式。PSACH是由软骨寡聚基质蛋白(COMP)基因突变引起的，而SEDC是由II型前胶原(COL2A1)基因突变引起的。我们报告一名儿童，由于PSACH和SEDC的联合表型而患有明显的骨骼发育不良。先证者的母亲患有PSACH，他的父亲患有SEDC。根据他的临床和放射学发现的严重性，该儿童被怀疑具有这两种表型，这一点通过分子分析得到了证实。COMP基因突变(C348R)虽然以前没有发表过，但在PSACH患者中是典型的，而COL2A1突变(T1370M)在某种程度上是非典型的，因为它预测了蛋白质羧基末端区域的氨基酸变化。这两个突变在这个家族中都有各自的表型。双重杂合子表型的描述和自然病史可能有助于家系关于风险和预后的咨询。(C)2001年Wiley-Liss，Inc.
Pseudoachondroplasia (PSACH) and spondyloepiphyseal dysplasia congenita (SEDC) are autosomal dominant forms of short-limb short stature caused by mutations in genes that encode structural components of the cartilage extracellular matrix. PSACH results from mutations in the cartilage oligomeric matrix protein (COMP) gene, while SEDC is caused by mutations in the gene for type II procollagen (COL2A1). We report a child with a distinct skeletal dysplasia due to the combined phenotypes of PSACH and SEDC. The proband's mother had PSACH and his father had SEDC. The child was suspected of having both phenotypes on the basis of the severity of his clinical and radiographic findings, and this was confirmed by molecular analysis. The COMP gene mutation (C348R), while not previously published, is typical of those in PSACH patients, whereas the COL2A1 mutation (T1370M) is somewhat atypical, as it predicts an amino acid change within the carboxyl-terminal region of the protein. Both mutations segregated with their respective phenotypes within this family. The description and natural history of the double heterozygote phenotype may be useful in counseling families regarding risk and prognosis. (C) 2001 Wiley-Liss, Inc.