The Department of Clinical Genetics, Helsinki University Hospital, HUSLAB, Helsinki, Finland.
Norio Centre, Rinnekoti Foundation, Helsinki, Finland.
Acta Ophthalmol. 2019 Dec;97(8):805-814. doi: 10.1111/aos.14128. Epub 2019 May 14.
To study the genetic aetiology and phenotypes of retinal degeneration (RD) in Finnish children born during 1993-2009.
Children with retinal degeneration (N = 68) were investigated during 2012-2014 with a targeted gene analysis or a next-generation sequencing (NGS) based gene panel. Also, a full clinical ophthalmological examination was performed.
The cohort covered 44% (68/153) of the Finnish children with inherited RD born 1993-2009. X-linked retinoschisis, retinitis pigmentosa, Leber congenital amaurosis and cone-rod dystrophy were the most common clinical diagnoses in the study group. Pathogenic mutations were found in 17 retinal genes. The molecular genetic aetiology was identified in 77% of the patients (in 77% of the families) analysed by NGS method. Several founder mutations were detected including three novel founder mutations c.148delG in TULP1, c.2314C>R (p.Gln772Ter) in RPGRIP1 and c.533G>A (Trp178Ter) in TYR. We also confirmed the previous tentative finding of c.2944 + 1delG in GYCU2D being the most frequent cause of Leber congenital amaurosis (LCA) in Finland.
Globally, RD is genetically heterogeneous with over 260 disease genes reported so far. This was shown not to be the case in Finland, where the genetic aetiology of RD is caused by a small group of genes, due to several founder mutations that are enriched in the population. We found that X-chromosomal retinoschisis constitutes the major group in Finnish paediatric RD population and is almost exclusively caused by two founder mutations. Several other founder mutations were detected including three novel founder mutations. All in all, the genetic aetiology of 77% of families was identified which is higher than previously reported from other populations, likely due to the specific genomic constitution of the Finns.
研究 1993 年至 2009 年期间芬兰出生的儿童视网膜变性（RD）的遗传病因和表型。
2012 年至 2014 年，对 68 例视网膜变性儿童进行靶向基因分析或下一代测序（NGS）基因谱分析。同时进行全面的临床眼科检查。
该队列涵盖了 1993 年至 2009 年期间芬兰遗传性 RD 患儿的 44%（68/153）。X 连锁性视网膜劈裂症、色素性视网膜炎、Leber 先天性黑矇和锥-杆营养不良是研究组中最常见的临床诊断。在通过 NGS 方法分析的患者（占分析家庭的 77%）中发现了 17 个视网膜基因的致病性突变。分子遗传学病因在 77%的患者（占分析家庭的 77%）中得到确定。检测到多个启动子突变，包括 TULP1 中的三个新启动子突变 c.148delG、RPGRIP1 中的 c.2314C>R（p.Gln772Ter）和 TYR 中的 c.533G>A（Trp178Ter）。我们还证实了先前关于 GYCU2D 中的 c.2944+1delG 是芬兰最常见的 Leber 先天性黑矇（LCA）病因的推测发现。
在全球范围内，RD 的遗传异质性很大，迄今为止已报道了 260 多个疾病基因。然而，芬兰的情况并非如此，RD 的遗传病因是由一小部分基因引起的，这些基因是由于人群中存在的几个启动子突变而富集的。我们发现，X 连锁性视网膜劈裂症构成了芬兰儿科 RD 人群的主要群体，几乎完全由两个启动子突变引起。还检测到其他几个启动子突变，包括三个新的启动子突变。总之，77%的家庭的遗传病因得到了确定，这比以前从其他人群报告的要高，可能是由于芬兰人的特定基因组构成所致。
