Two novel genetic associations with sector retinitis pigmentosa: USH2A and PRPF31

Sector retinitis pigmentosa (RP) is an attenuated phenotype in comparison to classic pan-retinal disease. The inferior retina is most often affected, though other quadrants may become involved with time, particularly with more damaging genetic variants. Sector RP has been described in association with several known genotypes, most commonly RHO. Case series of patients with a sector RP phenotype (and any affected family) and review of the literature. We describe two new genetic associations of sector RP: USH2A and PRPF31. Proband 1 had sector RP due to homozygous USH2A:c.13274C>T’ variants while proband 2 had sector RP due to a heterozygous PRPF31:c.351dup variant. There was significant intrafamilial variability in each pedigree. Though both variants are previously reported, the phenotype in those reports was not consistent with sector RP. The current USH2A pedigree is the first reported with the c.13274C>T’ variant homozygously, expressing a restricted, predominantly perivascular, sectoral RP. Non-syndromic USH2 genes have not previously been associated with sector RP. In the PRPF31 pedigree (c.351dup), the proband has restricted/sectoral disease but her daughter has classic pan-retinal RP. The cause of the attenuated phenotype and intrafamilial variability is unknown but could depend on several factors including occult modifier genes and environmental influences (e.g. light exposure to the inferior retina).节段性视网膜色素变性（Sector retinitis pigmentosa, RP）相较于经典的全视网膜型视网膜色素变性，属于表型减弱的亚型。视网膜下方象限最常受累，随着病程延长，其余视网膜象限也可受累，尤其是携带致病性更强的遗传变异的患者。节段性RP已被报道与多种已知基因型相关，其中最常见的为RHO基因。本研究针对携带节段性RP表型的患者（及受累家系）开展病例系列研究，并进行了文献复习。我们首次报道了节段性RP的两种新的遗传关联：USH2A基因与PRPF31基因。先证者1为纯合USH2A:c.13274C>T变异所致的节段性RP，先证者2则为杂合PRPF31:c.351dup变异所致的节段性RP。两个家系均存在显著的家系内表型异质性。尽管上述两种变异此前均已有报道，但既往报道中的表型均与节段性RP不符。本次报道的USH2A家系是首个携带纯合c.13274C>T变异、表现为局限性、以血管周分布为主的节段性RP的家系。此前尚无非综合征型USH2家族基因与节段性RP相关联的报道。在携带c.351dup变异的PRPF31家系中，先证者表现为局限性/节段性病变，但其女儿则表现为经典的全视网膜型RP。这种表型减弱及家系内表型异质性的具体发病机制尚不明确，但可能与多种因素相关，包括隐匿性修饰基因及环境影响（如视网膜下方区域的光照暴露）。