Novel mutation in RP2 gene in two brothers with X-linked retinitis pigmentosa and mtDNA mutation of leber hereditary optic neuropathy who showed marked differences in clinical severity

PURPOSE: To report the identification of a novel mutation of the RP2 gene in two Japanese brothers with X-linked retinitis pigmentosa of a differing clinical severity. The mother was a carrier of both retinitis pigmentosa and optic atrophy. METHODS: The older brother had a severe form of retinitis pigmentosa associated with macular degeneration and total optic atrophy, whereas the younger brother presented typical X-linked retinitis pigmentosa. RESULTS: Each patient exhibited a novel 2-bp insertion at codon 278 in exon 3 of the RP2 gene as well as a 11778 mutation in mitochondrial DNA. This suggests that the older brother may have developed Leber hereditary optic neuropathy as well as retinitis pigmentosa. CONCLUSION: Molecular testing confirmed the clinical diagnosis in each case. However, such testing did not explain the differences in the severity of the ophthalmoscopic findings between the two brothers.     

A novel homozygous Gly107Arg mutation in the RDH5 gene in a Japanese patient with fundus albipunctatus with sectorial retinitis pigmentosa

We examined the RDH5 gene for mutations in two unrelated Japanese families with fundus albipunctatus. Each proband with fundus albipunctatus in two families (family A's case was atypical with sectorial retinitis pigmentosa, while family B's case was typical), and 2 obligate carriers underwent molecular analysis of their RDH5 gene. DNA was amplified for all coding exons of the RDH5 gene with established primer pairs, and sequenced directly. Each family had a different mutation in the RDH5 gene. Family A had a homozygous mutation (Gly107Arg) while family B had a compound heterozygous mutation (Arg280His and Leu310GluVal). The obligate carriers were heterozygous with the wild-type and mutant-type alleles. The homozygous Gly107Arg mutation in the RDH5 gene described in this paper has not previously been described, though compound heterozygous mutations (Gly107Arg and Leu310GluVal) in the RDH5 gene have previously been reported.     

Genetic analysis of Chinese families reveals a novel truncation allele of the retinitis pigmentosa GTPase regulator gene

AIM: To make comprehensive molecular diagnosis for retinitis pigmentosa (RP) patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology. METHODS: A five-generation Han Chinese family diagnosed as non-syndromic X-linked recessive RP (XLRP) was recruited, including four affected males, four obligate female carriers and eleven unaffected family members. Capture-NGS was performed using a custom designed capture panel covers 163 known retinal disease genes including 47 RP genes, followed by the validation of detected mutation using Sanger sequencing in all recruited family members. RESULTS: Capture-NGS in one affected 47-year-old male reveals a novel mutation, c.2417_2418insG:p.E806fs, in exon ORF15 of RP GTPase regulator (RPGR) gene results in a frameshift change that results in a premature stop codon and a truncated protein product. The mutation was further validated in three of four affected males and two of four female carriers but not in the other unaffected family members. CONCLUSION: We have identified a novel mutation, c.2417_2418insG:p.E806fs, in a Han Chinese family with XLRP. Our findings expand the mutation spectrum of RPGR and the phenotypic spectrum of XLRP in Han Chinese families, and confirms Capture-NGS could be an effective and economic approach for the comprehensive molecular diagnosis of RP.     

原发性视网膜色素变性家系的RDS基因Pro216Leu突变及其表型研究

目的　研究原发性视网膜色素变性 (retinitispigmentosa ,RP)家系中缓慢型视网膜变性(retinaldegenerationslow ,RDS)患者的RDS基因突变与临床表型的关联 ,以探讨RP的发病机制。方法对来自同一家系的 2例RP患者及 2例正常人外周血DNA进行分子遗传学分析 ,采用聚合酶链反应(polymerasechainreaction ,PCR)及限制性片段长度多态性 (restrictionfragmentlengthpolymorphism ,RFLP)技术 ,筛查RDS基因突变 ,对有突变的RDS基因片段进行克隆测序及分析 ,同时进行家系分析及眼部临床检查。结果　来自同一家系的 2例RP患者均查出有RDS基因 2 16密码突变 ,而 2例正常人未查出上述突变。经测序证实RDS基因 2 16密码子的第 2个核苷酸出现了C→T的突变 (Pro2 16Leu)。RDS基因Pro2 16Leu突变的眼部临床表型为视力损害严重的弥漫型RP ,伴有黄斑部病变。结论　中国人RP患者存在RDS基因Pro2 16Leu突变 ;其眼部表型为弥漫型RP伴有黄斑部病变。     

Novel 2336-2337delCT mutation in RP1 gene in a Japanese family with autosomal dominant retinitis pigmentosa

PURPOSE: To determine the frequency and kinds of mutations in the RP1 gene, and to characterize the clinical features of a Japanese family with autosomal dominant retinitis pigmentosa (ADRP) with a novel 2336 to 2337delCT mutation in the RP1 gene. DESIGN: Case reports and results of DNA analysis. METHODS: Mutational screening by direct sequencing was performed on 96 unrelated patients with ADRP. The clinical features were determined by complete ophthalmologic examinations. RESULTS: A novel 2336 to 2337delCT mutation in the RP1 gene was identified in two patients from a Japanese family with ADRP. In addition, three families with ADRP carried a previously reported nonpathogenic Arg1933X mutation. The ophthalmic findings with a 2336 to 2337delCT mutation were similar to those of typical retinitis pigmentosa with rapid progression after age 40 years. CONCLUSIONS: The most common Arg677X mutation in the white population was not found in the Japanese population; instead a novel mutation was found.     

Rhodopsin gene codon 106 mutation (Gly-to-Arg) in a Japanese family with autosomal dominant retinitis pigmentosa

PURPOSE: To examine rhodopsin gene mutations in Japanese patients with retinitis pigmentosa. METHODS: We performed a mutational analysis of the rhodopsin gene in 42 patients from 40 families with retinitis pigmentosa. Genomic DNA was amplified by polymerase chain reaction (PCR) and the PCR products were sequenced. Restriction enzyme analysis was performed in family members of 1 patient with a rhodopsin gene mutation (Gly106Arg) and in 100 normal individuals. RESULTS: Among the patients with retinitis pigmentosa, 3 patients in one family had a heterozygous Gly106Arg mutation of the rhodopsin gene. They had night blindness and sectorial retinal dystrophy (predominantly at the inferior fundus) in both eyes. None of the 100 individuals with normal fundi had the Gly106Arg mutation of the rhodopsin gene. CONCLUSION: The Gly106Arg mutation of the rhodopsin gene has been found in Japanese patients with sectorial retinitis pigmentosa.     

X-linked retinitis pigmentosa in two families with a missense mutation in the RPGR gene and putative change of glycine to valine at codon 60

Objective

This study describes the ophthalmic findings in two unrelated white families with X-linked retinitis pigmentosa (XLRP) caused by a missense mutation in the retinitis pigmentosa GTPase regulator (RPGR) gene.

Design

Genetic screening and clinical correlation.

Participants

Thirty-six families with XLRP seen by the authors were screened for a possible mutation in the RPGR gene to identify three affected hemizygotes with retinitis pigmentosa and four heterozygote carriers in one family and one hemizygote and one carrier in a second family.

Intervention

All nine patients underwent a routine ocular examination, including slit-lamp biomicroscopy and a dilated fundus examination. Goldmann visual field kinetic perimetry, static threshold perimetry, and electroretinography also were obtained. The DNA screening was performed on the three affected male patients and four obligate carriers examined from one family and the two examined patients, plus an additional male and obligate carrier, from the second family to determine the presence of any causative mutation in the RPGR gene.

Main outcome measures

Findings on fundus examination, static threshold and kinetic perimetry, and electroretinography testing were the main outcome measures.

Results

A G→T nucleotide change at position 238 in exon 3 of the RPGR gene resulting in a putative substitute of Gly→Val at codon 60 was shown to segregate with RP in affected males and the carrier state in female heterozygotes in these two families. The ophthalmologic findings in hemizygotes as well as the carriers in this family were within the spectrum of findings characteristically noted in XLRP families. A tapetal-like reflex was not observed in any of the five female carriers. Psychophysical and electrophysiologic testing on the carriers indicated that cone and rod functions were impaired equivalently. When present in the carriers, visual field restriction was most apparent in, or limited to, the superotemporal quadrant, which corresponded to the retinal pigmentary changes that tended to occur in the inferonasal retina.

Conclusions

A mutation in exon 3 of the RPGR gene, which would result in a putative glycine to valine substitution at codon 60, is associated with a severe clinical phenotype in male patients and a patchy retinopathy without a tapetal-like reflex in carrier females. In these families, heterozygote carriers showed equivalent impairment of their cone and rod function.     

Screening for mutations in the IMPDH1 gene in Japanese patients with autosomal dominant retinitis pigmentosa

PURPOSE: To determine the presence and frequency of mutations in the IMPDH1 gene in Japanese patients with autosomal dominant retinitis pigmentosa (ADRP), and to characterize the clinical characteristics of patients with the Lys238Arg mutation in the IMPDH1 gene. DESIGN: Case reports and results of DNA analysis. METHODS: All 14 coding exons of the IMPDH1 gene were directly sequenced in 96 unrelated patients with ADRP. The clinical features were determined by visual acuity, slit-lamp biomicroscopy, and kinetic visual field tests. RESULTS: Two novel mutations, a Leu227Pro and Lys238Arg, in the IMPDH1 gene were identified in two unrelated families with ADRP. The clinical features associated with the Lys238Arg mutation were an early-onset and severe retinal degeneration. CONCLUSIONS: The most commonly reported Asp226Asn mutation was not found in the Japanese population, instead two novel mutations were found. These findings suggest that mutations of the IMPDH1 gene cause ADRP in the Japanese population.     

Late-onset central areolar choroidal dystrophy caused by a heterozygous frame-shift mutation affecting codon 307 of the peripherin/RDS gene

Mutations in the peripherin/RDS gene have been identified in families with various retinopathies including those affecting primarily the macula and those restricted to the retinal periphery. Here, we describe the clinical findings of two sisters with late-onset central areolar choroidal dystrophy (CACD). The two siblings underwent genetic testing and were found to be carriers of a heterozygous frame-shift mutation 920delT affecting codon 307 of the peripherin/RDS gene and resulting in a truncated, likely functionless, protein with an altered C-terminus (Leu307fsX83). The identical mutation has previously been reported to cause slowly progressive autosomal dominant retinitis pigmentosa. In our two patients, the Leu307fsX83 mutation accounts for an unusually mild form of retinal degeneration.     

Late-Onset Central Areolar Choroidal Dystrophy Caused by a Heterozygous Frame-Shift Mutation Affecting Codon 307 of the Peripherin/RDS Gene

Mutations in the peripherin/RDS gene have been identified in families with various retinopathies including those affecting primarily the macula and those restricted to the retinal periphery. Here, we describe the clinical findings of two sisters with late-onset central areolar choroidal dystrophy (CACD). The two siblings underwent genetic testing and were found to be carriers of a heterozygous frame-shift mutation 920delT affecting codon 307 of the peripherin/RDS gene and resulting in a truncated, likely functionless, protein with an altered C-terminus (Leu307fsX83). The identical mutation has previously been reported to cause slowly progressive autosomal dominant retinitis pigmentosa. In our two patients, the Leu307fsX83 mutation accounts for an unusually mild form of retinal degeneration.     

Peripherin/RDS gene mutation (Pro210Leu) and polymorphisms in Japanese patients with retinal dystrophies

PURPOSE: To determine the frequency of peripherin/RDS (retinal degeneration slow) gene mutations in Japanese patients with retinal dystrophies. METHODS: We analyzed the peripherin/RDS gene in 54 unrelated Japanese patients with retinal dystrophies. Genomic DNA was amplified by polymerase chain reaction (PCR) and the PCR products were sequenced. We also examined 100 healthy subjects, seeking mutations or variations of the peripherin/RDS gene. RESULTS: Of the 54 Japanese patients, one with retinitis pigmentosa had a heterozygous C to T change at the second nucleotide at codon 210 of exon 2 (CCT to CTT/Pro210Leu) of the peripherin/RDS gene. None of the 100 individuals with normal fundi had the Pro210Leu mutation of the peripherin/RDS gene. Three variants of the peripherin/RDS gene (GTC to GTT/Val106Val, Glu304Gln, and Gly338Asp) were also found. The first variation (GTC to GTT/Val106Val) was silent. Two concurrent missense variations (Glu304Gln and Gly338Asp) were seen in 25.9% of the affected patients and in 29% of the healthy individuals. CONCLUSION: A novel mutation (Pro210Leu) of the peripherin/RDS gene has been found in one Japanese patient with retinitis pigmentosa. The alterations of Val106Val, Glu304Gln, and Gly338Asp may be polymorphic variants in the Japanese population.     

Regional distribution of retinal degeneration in patients with the proline to histidine mutation in codon 23 of the rhodopsin gene.

Mutations in the rhodopsin gene are associated with as many as one quarter of all cases of autosomal dominant retinitis pigmentosa (RP). A number of different rhodopsin mutations have been reported but only the proline to histidine mutation in codon 23 (Pro-23-His) has been well characterized clinically. One recent report described a "sectoral" distribution of the retinal degeneration associated with this mutation, while another reported only that pigment was present in all four quadrants in 13 of 17 patients. This asymmetric distribution of pigmentation and visual field loss may prove to be an important clinical sign of a type of RP with a relatively good visual prognosis. The authors present a family with Pro-23-His rhodopsin-associated RP in which all six affected individuals had a regional distribution of the retinal degeneration in which the inferior hemisphere of the retina was most severely affected.     

一个X-连锁隐性遗传视网膜色素变性家系的RPGR基因新突变

目的 研究X-连锁隐性遗传视网膜色素变性(RP)家系RPGR基因突变男性患者和女性携带者的临床表型.方法 家系调查研究.收集RP先证者及其家系资料,完善眼科检查,抽取现存77名家系成员和80名正常对照者外周静脉血,提取DNA,进行聚合酶链反应(PCR),扩增RPGR基因外显子ORF15,扩增产物纯化后直接测序.结果 RP家系中,8例RP患者均为男性,呈隔代传递,不存在男性至男性的传递,患者的母亲及女儿都是致病基因携带者而不发病,符合X-连锁隐性遗传方式.在8例男性RP患者和14例女性致病基因携带者的RPGR基因外显子ORF15+577_578位点发现一个AG缺失突变,引起阅读框架的改变,该基因缺失突变在家系中共分离.AG缺失突变导致男性患者典型的RP改变,但发病时间和进展程度不一.携带有杂合型基因突变的14例女性携带者最具特征性的临床表型是中高度近视眼(-5.00～-22.00 D).结论 该RP家系患者由RPGR 基因外显子ORF15移码突变致g.ORF15+577_578delAG位点缺失.RPGR基因外显子ORF15的新突变可导致男性患者严重的RP表型,但女性致病基因携带者仅表现为中高度近视眼.(中华眼科杂志,2011,47:516-520)

Abstract：

Objective To screen the mutation in the RPGR gene in a large Chinese family with X-linked recessive retinitis pigmentosa (RP) and to describe the phenotype in affected males and female carriers. Methods Ophthalmic examinations were performed in 77 family members of a RP pedigree to identify affected individuals. Polymerase chain reaction (PCR) and direct sequencing were used for screening of mutations in RPGR gene exon ORF15. Results Mutation screening demonstrated a novel mutation, g.ORF15+577_ 578delAG, which caused an open reading frameshift and resulted in premature truncation of the RPGR protein. This mutation was detected in 8 affected male individuals and 14 obligate female carriers in this family and was found to segregate with the phenotype in this family. This mutation led to a severe RP phenotype in male affected individuals with some variability in the age of onset of night blindness and loss of visual acuity, but was recessive in female carriers without a RP phenotype. However the most striking phenotypic feature in female carriers in this pedigree was moderate to high myopia with refractive error ranging from -5.00 D to -22.00 D in 14 female carriers. Conclusions This novel mutation in RPGR ORF15 causes serious RP phenotype in males and no RP phenotype in female carriers. Moderate to high myopia was a particular feature for female carriers in this pedigree. Our finding expands the spectrum of RPGR mutations causing RP and phenotypic spectrum of the disease in Chinese family, which is useful for further genetic consultation and genetic diagnosis.     

Mutations in the gene coding for guanylate cyclase-activating protein 2 (<Emphasis Type="Italic">GUCA1B</Emphasis> gene) in patients with autosomal dominant retinal dystrophies

Background We investigated mutations in the gene coding for guanylate-cyclase activating protein 2 (GCAP2), also known as GUCA1B gene, in Japanese patients with retinitis pigmentosa (RP) and tried to identify phenotypic characteristics associated with mutations in the gene.Subjects and methods Genomic DNA samples from 63 unrelated patients with autosomal dominant retinitis pigmentosa (ADRP) and 33 patients with autosomal recessive retinitis pigmentosa (ARRP) were screened by single-strand conformational polymorphism analysis followed by direct sequencing. Clinical features associated with a mutation were demonstrated by visual acuity, visual field testing, fundus photography, and electroretinography.Results A novel transitional mutation converting GGA to AGA at codon 157 (G157R) was identified. This mutation has been found in three index patients from three independent families. Phenotypic examination of seven members of the three families revealed that this mutation was associated with RP with or without macular involvement in five members, macular degeneration in one member, and asymptomatic normal phenotype in one member. In addition, previously unknown polymorphic changes including V29V, Y57Y, T87I, and L180L were identified.Conclusions A racial difference exists in the spectrum of mutations and/or polymorphisms in the GCAP 2 gene between British and Japanese populations. Our findings suggest that the mutation in the GCAP 2 gene can cause one form of autosomal dominant retinal dystrophy, with variable phenotypic expression and incomplete penetrance.     

Novel deletion of the RPGR gene in a Chinese family with X-linked retinitis pigmentosa

Purpose: To characterize a Chinese family with inherited retinitis pigmentosa (RP). Methods: Linkage studies and haplotype analysis were used for gene mapping, and single-strand conformation polymorphism (SSCP) analysis and direct DNA sequence analysis were used for identifying the responsible mutation. Results: Pedigree analysis suggests that RP in the Chinese family RP002 is inherited either as an autosomal recessive trait or as an X-linked trait. Linkage analysis of RP002 excluded all known autosomal recessive RP loci. Further analysis with 17 polymorphic markers covering the entire X chromosome localized the RP gene in RP002 between markers GATA175D03 and GATA144D04 on Xp11.4, a region where the RP3 gene ( RPGR ) is found. Mutation analysis of the RPGR gene in RP002 revealed a novel 28-bp deletion in exon 7. This deletion resulted in an in-frame stop codon that eliminates the C-terminal two-thirds of the RPGR protein. The 28-bp deletion co-segregated with the disease in the family and was not present in 100 normal Chinese individuals. Female carriers of the deletion were affected with myopia and had ERG abnormalities and mild constriction of visual field. Conclusions: A novel 28-bp deletion in the RPGR gene identified in an X-linked Chinese RP family causes severe RP in male patients as well as myopia and ERG abnormalities in female carriers. The deletion represents the largest microdeletion identified in RPGR to date, and expands the spectrum of RPGR mutations causing XLRP.     

Genotype-phenotype correlation in a family with Arg135Leu rhodopsin retinitis pigmentosa

AIM: To describe the clinical characteristics and disease course of a large family with retinitis pigmentosa (RP) from an Arg135Leu change in rhodopsin. METHODS: 29 patients in this family were evaluated. Goldmann visual fields were performed on 14 affected individuals, Ganzfeld electroretinography (ERG) on eight individuals (11-56 years), and blood samples collected on 10 individuals (11-58 years). Patient visual field data were compared with previously reported patients with different rhodopsin mutations using linear regression. RESULTS: An Arg135Leu mutation was identified in rhodopsin. Distinct stages of clinical evolution were identified for this family ranging from normal, white dots, classic bone spicules and, finally, ending with extensive retinal pigment epithelium (RPE) atrophy. 9/16 patients over the age of 20 years also demonstrated marked macular atrophy. All patients who underwent full field ERG testing demonstrated non-recordable ERGs. The overall regression model comparing solid angles of visual fields from patients with rhodopsin mutations (Pro23His, Pro347Ala, Arg135Leu) shows significant effects for age (p = 0.0005), mutation (p = 0.0014), and interaction between age and mutation (p = 0.018) with an R(2) of 0.407. CONCLUSIONS: An Arg135Leu change in rhodopsin results in a severe form of RP that evolves through various fundus appearances that include white dots early in life and classic appearing RP later. This transmembrane change in rhodopsin proves to be more severe than in a family with an intradiscal change and a family with a cytoplasmic change.     

Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa

PURPOSE: To determine the disease expression in heterozygotes for mutations in the RP1 gene, a newly identified cause of autosomal dominant retinitis pigmentosa (adRP). METHODS: Screening strategies were used to detect disease-causing mutations in the RP1 gene, and detailed studies of phenotype were performed in a subset of the detected RP1 heterozygotes using electroretinography (ERG), psychophysics, and optical coherence tomography (OCT). RESULTS: Seventeen adRP families had heterozygous RP1 changes. Thirteen families had the Arg677ter mutation, whereas four others had one of the following: Pro658 (1-bp del), Ser747 (1-bp del), Leu762-763 (5-bp del), and Tyr1053 (1-bp del). In Arg677ter RP1 heterozygotes, there was regional retinal variation in disease, with the far peripheral inferonasal retina being most vulnerable; central and superior temporal retinal regions were better preserved. The earliest manifestation of disease was rod dysfunction, detectable as reduced rod ERG photoresponse maximum amplitude, even in heterozygotes with otherwise normal clinical, functional, and OCT cross-sectional retinal imaging results. At disease stages when cone abnormalities were present, there was greater rod than cone dysfunction. Patients with the RP1 frameshift mutations showed similarities in phenotype to those with the Arg677ter mutation. CONCLUSIONS: Earliest disease expression of RP1 gene mutations causing adRP involves primarily rod photoreceptors, and there is a gradient of vulnerability of retinopathy with more pronounced effects in the inferonasal peripheral retina. At other disease stages, cone function is also affected, and severe retina-wide degeneration can occur. The nonpenetrance or minimal disease expression in some Arg677ter mutation-positive heterozygotes suggests important roles for modifier genes or environmental factors in RP1-related disease.     

A novel RPGR exon ORF15 mutation in a family with X-linked retinitis pigmentosa and Coats'-like exudative vasculopathy

PURPOSE: To describe the ophthalmic and genetic findings in a family with X-linked retinitis pigmentosa (RP) and Coats'-like exudative vasculopathy. DESIGN: Observational case series. METHODS: Family members underwent comprehensive ophthalmologic examination. Leukocyte genomic DNA samples were obtained and screened for RPGR (RP3) mutations by direct polymerase chain reaction sequencing. RESULTS: The proband had RP with bilateral Coats'-like vasculopathy and was treated with fluorescein-potentiated argon laser therapy. The findings in two other affected male patients and three obligate carrier female patients were within the clinical spectrum of a typical X-linked-recessive RP. A novel nonsense RPGR exon ORF15 mutation (912G>T) was found to segregate with RP in this family. CONCLUSIONS: This report expands the clinical heterogeneity spectrum caused by RPGR mutations and our knowledge concerning the molecular pathologic condition that pertains to Coats'-like RP. Consistent with the literature, Coats' response was not observed in all family members who were affected by RP, which suggests the involvement of other genetic and/or environmental factors.     

The 208delG mutation in FSCN2 does not associate with retinal degeneration in Chinese individuals

PURPOSE: The 208delG (c.72delG, p.Thr25GlnfsX120) mutation in the FSCN2 gene was reported to cause autosomal dominant retinitis pigmentosa (ADRP) and autosomal dominant macular degeneration (ADMD). The purpose of this study was to detect the 208delG mutation in Chinese individuals, with or without hereditary retinal degeneration. METHODS: DNA fragments encompassing the 208delG mutation were amplified by polymerase chain reaction (PCR). The amplicons were analyzed by sequencing or/and heteroduplex- single-strand conformational polymorphism (SSCP) analysis. An ophthalmic evaluation was conducted in those individuals with the 208delG mutation. RESULTS: The 208delG mutation was detected in 8 of 242 unrelated probands: 175 with retinitis pigmentosa (RP), 20 with Leber congenital amaurosis (LCA), and 47 with cone-rod dystrophy (CORD). Of the eight, the retinal diseases were RP in six probands, LCA in one proband, and CORD in one proband. The disease was transmitted as an autosomal dominant (one family), autosomal recessive (two families), or sporadic (five families) trait. The mutation did not cosegregate with retinal degeneration in three families, whereas five normal family members also had the mutation. In addition, this mutation was also detected in 13 of 521 unrelated control subjects. CONCLUSIONS: The 208delG mutation in FSCN2 is not associated with hereditary retinal degeneration in the Chinese individuals examined, which contradicts the original report about mutation in FSCN2 as a cause of ADRP and ADMD. This finding reminds us that great care is needed in making mutation-disease associations.