Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Molecular Genetics and Preventive Medicine, University of Messina, via C. Valeria 1, I-98125, Messina, Italy.
Department of Cutting-Edge Medicine and Therapies, Biomolecular Strategies and Neuroscience, Section of Neuroscience-applied Molecular Genetics and Predictive Medicine, I. E. ME. S. T, via Michele Miraglia 20, I-90139, Palermo, Italy.
Hum Genomics. 2017 Aug 1;11(1):18. doi: 10.1186/s40246-017-0114-6.
Autosomal recessive forms of retinitis punctata albescens (RPA) have been described. RPA is characterized by progressive retinal degeneration due to alteration in visual cycle and consequent deposit of photopigments in retinal pigment epithelium. Five loci have been linked to RPA onset. Among these, the retinaldehyde-binding protein 1 gene, RLBP1, is the most frequently involved and several founder mutations were reported. We report results of a genetic molecular investigation performed on a large Sicilian family in which appears a young woman with RPA.
The proband is in homozygous condition for a novel RLBP1 single-pair deletion, and her healthy parents, both heterozygous, are not consanguineous. Thenovelc.398delC (p.P133Qfs*258) involves the exon 6 and leads to a premature stop codon, resulting in a truncated protein entirely missing of CRAL-TRIO lipid-binding domain. Pedigree analysis showed other non-consanguineous relatives heterozygous for the same mutation in the family. Extension of mutation research in the native town of the proband revealed its presence also in healthy subjects, in a heterozygous condition.
A novel RLBP1 truncating mutation was detected in a young girl affected by RPA. Although her parents are not consanguineous, the mutation was observed in a homozygous condition. Being them native of the same small Sicilian town of Fiumedinisi, the hypothesis of a geographical area-related mutation was assessed and confirmed.
已描述常染色体隐性形式的白点状视网膜营养不良（RPA）。RPA 的特征是由于视觉循环改变和随后在视网膜色素上皮中沉积光色素而导致进行性视网膜变性。已经有五个位点与 RPA 发病相关。在这些中，视黄醛结合蛋白 1 基因，RLBP1 是最常涉及的，并且已经报道了几个创始人突变。我们报告了对一个大型西西里家族进行的遗传分子研究的结果，该家族中有一名患有 RPA 的年轻女性。
先证者为 RLBP1 单对缺失的纯合子，而她健康的父母均为杂合子，且无血缘关系。该 novelc.398delC (p.P133Qfs*258) 涉及外显子 6，导致提前终止密码子，从而产生完全缺失 CRAL-TRIO 脂质结合域的截短蛋白。家系分析显示，家族中其他非近亲的亲属为同一突变的杂合子。在先证者的原籍镇扩展突变研究显示，该突变也存在于健康人群中，为杂合子状态。
在一名患有 RPA 的年轻女孩中检测到一种新的 RLBP1 截断突变。尽管她的父母没有血缘关系，但该突变以纯合子状态存在。由于他们都来自西西里小镇 Fiumedinisi，因此评估并证实了与地理区域相关的突变假说。
