Somatic and gonadal mosaicism in x-linked retinitis pigmentosa
Somatic and gonadal mosaicism in x-linked retinitis pigmentosa
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DOI：
10.1002/ajmg.a.31984
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发表时间：
2007-11-01
影响因子：
2
通讯作者：
Nao-i, Nobuhisa
中科院分区：
文献类型：
--
作者：
Jin, Zi-Bing;Gu, Feng;Nao-i, Nobuhisa
RPGR基因中的g.ORF15 + 652- 653 delAG突变是X连锁视网膜色素变性（XLRP）中最常见的突变。本研究的目的是调查在XLRP家庭嵌合的可能性。招募了RP家族中的8名受试者。采集血样用于DNA提取。对RPGR基因进行单倍型分析和突变筛查。此外，先证者的母亲的毛囊和颊细胞的样品被用于DNA提取和分子分析。通过常规眼科检查、Goldmann视野检查、视网膜电图和彩色眼底照相来表征表型。在第二代和第三代患者/携带者中鉴定出g.ORF15+ 652- 653 delAG突变。第一代女性，谁被认为是一个专性携带者，表现出正常的表型，以及正常的基因型淋巴细胞DNA，表明性腺嵌合体，然而，杂合AG-缺失在652和653核苷酸被确定在毛囊，毛干和颊细胞的基因组DNA，表明突变是体细胞。总之，我们报告了一个家庭中，一个无症状的妇女与体细胞-性腺嵌合体的RPGR基因突变传递突变的无症状的女儿和儿子与XLRP。性腺嵌合体可能导致一定比例的多重或单一RP家族，其中发现超过50%的RP病例。
The g.ORF15 + 652-653delAG mutation in the RPGR gene is the most frequent mutation in X-linked retinitis pigmentosa (XLRP). The objective of this study was to investigate the possibility of mosaicism in an XLRP family. Eight subjects in the RP family were recruited. Blood samples were collected for DNA extraction. Haplotype analysis and mutational screening on the RPGR gene were performed. Additionally, samples of hair follicles and buccal cells from the mother of the proband were acquired for DNA extraction and molecular analysis. Phenotype was characterized with routine ophthalmic examination, Goldmann perimetry, electroretinography, and color fundus photography. A g.ORF15+ 652-653delAG mutation was identified in second- and third-generation patients/carriers. A first-generation female, who was considered to be an obligate carrier, demonstrated a normal phenotype as well as a normal genotype in lymphocytic DNA, indicating the gonadal mosaicism; however, a heterozygous AG-deletion at nucleotide 652 and 653 was identified in the genomic DNA of hair follicles, hair shaft, and buccal cells, indicating that the mutation is somatic. In conclusion, we reported on a family in which an asymptomatic woman with somatic-gonadal mosaicism for a RPGR gene mutation transmitted the mutation to an asymptomatic daughter and to a son with XLRP. Gonadal mosaicism may be responsible for a proportion of multiplex or simplex RP families, in which more than 50% of all cases of RP are found. (c) 2007 Wiley-Liss, Inc.