Rhizomelic Chrondrodysplasia Punctata Type 2 Resulting From Paternal Isodisomy of Chromosome 1
Rhizomelic Chrondrodysplasia Punctata Type 2 Resulting From Paternal Isodisomy of Chromosome 1
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DOI：
10.1002/ajmg.a.33489
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发表时间：
2010-07-01
影响因子：
2
通讯作者：
Braverman, Nancy
中科院分区：
文献类型：
--
作者：
Nimmo, Graeme;Monsonego, Sarah;Braverman, Nancy
Rhizomelic chondrodysplasia punctata（RCDP）是一种常染色体隐性遗传疾病，由醚脂质生物合成所必需的三个过氧化物酶体基因之一突变引起，PEX 7（RCDP 1），GNPAT（RCDP 2）和AGPS（RCDP 3）。受影响的患者具有特征性特征，包括近端长骨缩短、骨骺点彩、双侧白内障、生长和发育迟缓。大多数患者为1型RCDP，约5%为2型或3型RCDP。我们确定了一个病人与RCDP 2型和一个明显的纯合缺失，c.1428delC，他的GNPAT基因全测序后。父亲是这种突变的杂合子，而母亲GNPAT基因的测序显示只有野生型序列。对亲本gDNA进行的Southern分析未显示母体基因缺失的证据。扩增和片段分析的二核苷酸重复标记跨越1号染色体的患者和父母双方揭示了父系单亲遗传。我们讨论了造成单亲二体（UPD）在这个病人的潜在机制，并回顾了1号染色体UPD的文献。该患者无非RCDP临床特征，这与支持1号染色体上无印记基因的既往文献一致。这是第一次描述由UPD引起的RCDP，它极大地改变了父母复发的风险，突出了当先证者通过序列分析具有推定的纯合突变时获得父母基因型的价值。(C)2010 Wiley-Liss，Inc.
Rhizomelic chondrodysplasia punctata (RCDP) is an autosomal-recessive disorder resulting from mutations in one of three peroxisomal genes essential for ether lipid biosynthesis, PEX7 (RCDP1), GNPAT (RCDP2), and AGPS (RCDP3). Affected patients have characteristic features including shortening of the proximal long bones, epiphyseal stippling, bilateral cataracts, growth and developmental delays. Whereas the majority of patients have RCDP type 1, around 5% have RCDP type 2 or 3. We identified a patient with RCDP type 2 and an apparent homozygous deletion, c.1428delC, after full sequencing of his GNPAT genes. The father was heterozygous for this mutation, while sequencing of the maternal GNPAT genes revealed only wild-type sequence. Southern analyses performed on parental gDNA did not show evidence of a maternal gene deletion. Amplification and fragment analysis of dinucleotide repeat markers spanning chromosome 1 in the patient and both parents revealed paternal uniparental inheritance. We discuss the potential mechanisms causing uniparental disomy (UPD) in this patient and review the literature on chromosome 1 UPD. The absence of non-RCDP clinical features in this patient was consistent with previous literature supporting the absence of imprinted genes on chromosome 1. This first description of RCDP caused by UPD dramatically changes the parental recurrence risk, highlighting the value of obtaining parental genotypes when the proband has a putative homozygous mutation by sequence analysis. (C) 2010 Wiley-Liss, Inc.