X-linked juvenile retinoschisis: mutations at the retinoschisis and Norrie disease gene loci?

Hiraoka, Miki; Rossi, Fábio; Trese, Michael T.; Shastry, Barkur S.

doi:10.1007/s100380170108

Cited by 8 publications

(5 citation statements)

References 17 publications

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“…1) harboring missense mutations (parent-offspring pair, family 1) and nonsense mutations (sib-sib pair, family 2) in the rS1 gene and exhibiting variations in clinical phenotype. Mutational analyses and the clinical phenotypes of these families were previously reported (14,15), and are summarized in Table i. For genotype analysis, blood samples were collected, and leukocyte dnas were isolated.…”

Section: Methodsmentioning

confidence: 99%

Common polymorphisms of the CFH, LOC 387715/ARMS2 and HTRA1 genes may not influence the intra-familial variability of X-linked juvenile retinoschisis

Shastry

2010

Mol Med Rep

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Abstract. X-linked juvenile retinoschisis (XlrS) is the leading cause of juvenile macular degeneration in males and is rare in females. Previous studies have shown that there is a marked intra-and inter-familial variation in disease severity and progression. This suggests that additional factors, such as genetic modifiers and environmental elements, influence disease severity. in order to understand the contribution of genetic modifiers, we aimed to ascertain whether common variants of the cFH, loc 387715/arMS2 and HTra1 genes, which are major risk factors in age-related macular degeneration, contribute to the phenotypic variability of the XlrS disorder. Two unrelated XlrS families were selected, one harboring the missense mutation and the second a nonsense mutation in the rS gene. Both families exhibited variations in clinical phenotype. Genomic dna from family members were analyzed for the above three genes using the polymerase chain reaction-based restriction fragment length polymorphism method. our analyses revealed that both families were wild-type with respect to the loc 387715/arMS2 and HTra1 genes. in one family (but not the other), the most severely affected and unaffected individuals were heterozygous for the cFH polymorphisms, while the less severely affected individual was wild-type. However, this alteration did not necessarily influence disease severity. Although we cannot completely rule out the role of the above genes in determining the phenotypic variability of the disorder, and though the statistical significance of the results could not be assessed due to the small scale of the study, it is unlikely that common polymorphisms of the cFH, loc 387715/arMS2 and HTRA1 genes serve as disease modifiers of the XLRS disorder. IntroductionX-linked juvenile retinoschisis (XlrS), also known as congenital retinoschisis (rS), is a relatively rare recessively inherited bilateral vitreoretinal disorder that develops early in life. it is the leading cause of juvenile macular degeneration in males, and is rare in females. However, homozygous females and even, in rare cases, heterozygous females, may be affected (1). in the majority of cases, carriers have normal vision and cannot be identified by clinical means alone. The condition is characterized by the splitting of the superficial layer of the sensory retina in addition to macular degeneration (reviewed in ref.2). Peripheral schisis may also occur in 50% of cases (3). The disorder is clinically variable, and its prevalence ranges from 1:5,000 to 1:25,000. Visual impairment is usually mild in the early stages, but in the later stage vitreal hemorrhages, retinal detachment and occasionally neovascular glaucoma may develop, which may lead to blindness. The biochemical abnormality of rS is beginning to be understood.Linkage mapping has allowed the identification and isolation of the gene underlying rS (termed rS1 or XlrS1), of which over 150 mutations have been reported (4,5). The rS1 gene encodes a secreted protein and is expressed specifically in photoreceptors...

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Section: Methodsmentioning

confidence: 99%

Common polymorphisms of the CFH, LOC 387715/ARMS2 and HTRA1 genes may not influence the intra-familial variability of X-linked juvenile retinoschisis

Shastry

2010

Mol Med Rep

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“…In addition, RS1 and NDP digenic inheritance have been reported in families with retinoschisis. [ 43 ] A novel RS1 gene mutation (c. 375_377 del AGA) was identified in a rare clinical phenotype of X-linked retinoschisis in an angle-closure glaucoma patient of Indian origin. [ 44 ] Unusual clinical manifestations of JXLR can be characterized by a combination of ERG, OCT, and family screening.…”

Section: Juvenile X-linked Retinoschisis (Jxlr)mentioning

confidence: 99%

Rare eye diseases in India: A concise review of genes and genetics

Jeyabalan

Ghosh²,

Mathias³

et al. 2022

Indian Journal of Ophthalmology

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Rare eye diseases (REDs) are mostly progressive and are the leading cause of irreversible blindness. The disease onset can vary from early childhood to late adulthood. A high rate of consanguinity contributes to India’s predisposition to RED. Most gene variations causing REDs are monogenic and, in some cases, digenic. All three types of Mendelian inheritance have been reported in REDs. Some of the REDs are related to systemic illness with variable phenotypes in affected family members. Approximately, 50% of the children affected by REDs show associated phenotypes at the early stages of the disease. A precise clinical diagnosis becomes challenging due to high clinical and genetic heterogeneity. Technological advances, such as next-generation sequencing (NGS), have improved genetic and genomic testing for REDs, thereby aiding in determining the underlying causative gene variants. It is noteworthy that genetic testing together with genetic counseling facilitates a more personalized approach in the accurate diagnosis and management of the disease. In this review, we discuss REDs identified in the Indian population and their underlying genetic etiology.

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“…Though genetic loci for retinoschisis (Xp22.13) and Norrie disease (Xp1.3) are distinct from each other, a knock-out mouse model of ND has been shown to exhibit retinoschisis-like alterations [2,10,18]. And, there is a report on familial retinoschisis patients harboring digenic variations in RS1 and NDP genes, yet, segregating only with XLRS pathology [19]. It is further intriguing to note that certain ocular features like retrolental fibrovascular membrane, retinal traction, and retinal detachment are common features of both the disorders [20].…”

Section: Introductionmentioning

confidence: 99%

Retinoschisis and Norrie Disease: A missing link

Rajendran

Chidambaram

Nagarajan

et al. 2021

Preprint

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Objective: Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein-protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship. Result: Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.

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X-linked juvenile retinoschisis: mutations at the retinoschisis and Norrie disease gene loci?

Cited by 8 publications

References 17 publications

Common polymorphisms of the CFH, LOC 387715/ARMS2 and HTRA1 genes may not influence the intra-familial variability of X-linked juvenile retinoschisis

Common polymorphisms of the CFH, LOC 387715/ARMS2 and HTRA1 genes may not influence the intra-familial variability of X-linked juvenile retinoschisis

Rare eye diseases in India: A concise review of genes and genetics

Retinoschisis and Norrie Disease: A missing link

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