Nonsyndromic Retinitis Pigmentosa in the Ashkenazi Jewish Population
这篇文章是Corhort
【摘要学习】
Purpose:
To analyze the genetic and clinical findings in retinitis pigmentosa (RP) patients of Ashkenazi Jewish (AJ) descent, aiming to identify genotypeephenotype correlations.
【分析Ashkenazi犹太人（AJ）血统的视网膜色素变性（RP）患者的遗传和临床表现，旨在鉴定基因型与表型的相关性】
Design: Cohort study.
Participants:
Retinitis pigmentosa patients from 230 families of AJ origin.
Methods: Sanger sequencing was performed to detect specific founder mutations known to be prevalent in the AJ population. Ophthalmologic analysis included a comprehensive clinical examination, visual acuity (VA), visual fields, electroretinography, color vision testing, and retinal imaging by OCT, pseudocolor, and auto fluorescence fundus photography.
【一代测序以检测已知在AJ人群中普遍存在的突变。眼科检查包括全面的临床检查，视力（VA），视野，视网膜电图，色觉测试以及通过OCT和自发荧光眼底照相术进行的视网膜成像】
Main Outcome Measures: Inheritance pattern and causative mutation; retinal function as assessed by VA,visual fields, and electroretinography results; and retinal structural changes observed on clinical funduscopy aswell as by pseudocolor, autofluorescence, and OCT imaging.
Results: The causative mutation was identified in 37% of families. The most prevalent RP-causing mutations are the Alu insertion (c.1297_8ins353, p.K433Rins31*) in the male germ cell-associated kinase (MAK) gene (39% of families with a known genetic cause for RP) and c.124A>G, p.K42E in dehydrodolichol diphosphate syn（39％的RP的家庭已知遗传原因是）中的Alu插入和c.124A >G，p.K42E在脱氢二氢二磷酸二磷酸合酶（DHDDS）中的含量（33％）}Additionally, disease-causing mutations were identified in 11 other genes. Analysis of clinical parameters of patients with mutations in the 2 most common RP-causing genes revealed that MAK patients had better VA and visual fields at relatively older ages in comparison with DHDDS patients. Funduscopic findings of DHDDS patients matched those of MAK patients who were 20 to 30 years older. Patients with DHDDS mutations were referred for electrophysiologic evaluation at earlier ages, and their cone responses became nondetectable at a much younger age than MAK patients.
对两个最常见的引起RP的基因突变的患者的临床参数进行分析后发现，与DHDDS患者相比，MAK患者在相对较高的年龄时具有更好的VA和视野。
DHDDS患者的眼底镜检查结果与年龄在20至30岁的MAK患者的眼底观察结果相匹配。具有DHDDS突变的患者在较早的年龄就被转介进行电生理评估，并且其锥体反应在比MAK患者年轻得多的年龄就变得不可检测
Conclusions: Our AJ cohort of RP patients is the largest reported to date and showed a substantial difference in the genetic causes of RP compared with cohorts of other populations, mainly a high rate of autosomal recessive inheritance and a unique composition of causative genes. The most common RP-causing genes in our cohort, MAK and DHDDS, were not described as major causative genes in other populations. The clinical data show that in general, patients with biallelic MAK mutations had a later age of onset and a milder retinal phenotype compared with patients with biallelic DHDDS mutations.
与其他人群相比，本队列的RP的遗传原因显示出显着差异，主要是常染色体隐性遗传率高和致病基因的独特组成。在我们的队列中，最常见的引起RP的基因MAK和DHDDS在其他人群中未被描述为主要致病基因。临床数据表明，与双等位基因DHDDS突变患者相比，双等位基因MAK突变患者的发病年龄更大，视网膜表型更轻。
【METHODS】
【主要学习他基因分析的步骤】
Genetic Analysis
DNA was extracted from the index patient, as well as from other affected and unaffected family members, with the FlexiGene DNA kit (QIAGEN) or by the Maxwell 16 Blood DNA purification kit(AS1010; Promega, Madison, WI) using the Maxwell 16 instrument (Promega).
【KEY RESULTS】
【CONCLUSION】
【COMMENTS】
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