Complete paternal uniparental isodisomy of chromosome 1: A novel mechanism for Herlitz junctional epidermolysis bullosa
Complete paternal uniparental isodisomy of chromosome 1: A novel mechanism for Herlitz junctional epidermolysis bullosa
复制标题
DOI：
10.1046/j.1523-1747.2000.00052.x
复制
发表时间：
2000-08-01
影响因子：
6.5
通讯作者：
Uitto, J
中科院分区：
文献类型：
--
作者：
Takizawa, Y;Pulkkinen, L;Uitto, J
单亲二倍体是指个体从单亲遗传了特定染色体的两个拷贝的情况。在极少数情况下，单亲二体性已被证明与隐性遗传性疾病的发病机制有关。在此，我们报告了一名患有赫利茨交界性大疱性表皮松解症的日本患者（OMIM 编号 226700），该患者在 8 个月大时死于该疾病的并发症。突变分析显示，先证者是编码层粘连蛋白5的γ2链的LAMC2基因中的无义突变C553X的纯合子。父亲是该突变的杂合携带者，而母亲有该基因的两个正常等位基因。该患者的 LAMC2 基因中 15 个已知的基因内多态性显示出纯合性。此外，使用跨越整个 1 号染色体的 16 个微卫星标记对父母和先证者进行的基因型分析显示，患者的所有测试标记都是纯合的，并且这些等位基因源自父亲。在 16 个标记中，有 8 个标记能够充分说明先证者不存在母体 1 号染色体，这表明该患者具有完全的父本染色体二倍体。因此，该患者的 Herlitz 交界性大疱性表皮松解症表型是由纯合 LAMC2 突变 C553X 引起的，该突变是父系起源，是非分离和涉及单体拯救的单亲二体性的结果。这是一种导致赫利茨交界性大疱性表皮松解症的新机制，对评估后续妊娠的风险具有重要意义。
Uniparental disomy denotes a situation when an individual has inherited two copies of a specific chromosome from a single parent. Uniparental disomy has been demonstrated to be involved in the pathogenesis of recessively inherited diseases in rare cases. Here we report a patient of Japanese origin with Herlitz junctional epidermolysis bullosa (OMIM no. 226700), who died at the age of 8 mo from complications of the disease. The mutation analysis revealed that the proband was homozygous for a nonsense mutation C553X in the LAMC2 gene encoding the gamma 2 chain of laminin 5. The father was a heterozygous carrier of this mutation whereas the mother had two normal alleles of this gene. The patient showed homozygosity for 15 known intragenic polymorphisms in the LAMC2 gene. Furthermore, genotype analysis, performed from the parents and the proband, using 16 microsatellite markers spanning the entire chromosome 1, revealed that the patient was homozygous for all markers tested, and that these alleles originated from the father. Among the 16 markers, eight were fully informative for the absence of the maternal chromosome 1 in the proband, suggesting that the patient had complete paternal isodisomy of this chromosome. Thus, the Herlitz junctional epidermolysis bullosa phenotype in this patient is caused by homozygous LAMC2 mutation C553X that is of paternal origin and results from nondisjunction and uniparental disomy involving monosomy rescue. This is a novel mechanism resulting in Herlitz junctional epidermolysis bullosa and has implications for assessment of the risk in subsequent pregnancies.