Early occurrence of primary angle-closure glaucoma in a patient with retinitis pigmentosa and CRB1 gene variations / Manifestação precoce de glaucoma de ângulo fechado em paciente com retinopatia por mutação no gene CRB1

ABSTRACT We describe the case of a 15-year-old girl with decreased visual acuity associated with elevated intraocular pressure in both eyes and angle closure on gonioscopy. She also presented attenuation of retinal vessels and optic disc pallor with large excavation in the left eye. Ultrasound biomicroscopy revealed an anteriorly positioned ciliary body and absence of ciliary sulcus, confirming the plateau iris configuration. Spectral-domain optical coherence tomography revealed a bilateral cystoid macular edema. Genetic screening revealed heterozygous variants of the Crumbs homolog 1 (CRB1) gene (c.2843G>A and c.2506C>A). The patient underwent trabeculectomy for intraocular pressure control and topical treatment for macular edema. This case highlights the importance of performing gonioscopy and evaluating intraocular pressure in patients with a shallow anterior chamber despite young age. In addition, it also shows the importance of genetic screening, when available, in elucidating the diagnosis and providing patients and their families' information on the patient's prognosis and possible therapeutic options.

RESUMO Nós descrevemos um caso de uma paciente de 15 anos com queda de acuidade visual e aumento da pressão intraocular em ambos os olhos, juntamente com fechamento angular no exame de gonioscopia. Na fundoscopia a paciente apresentava atenuação dos vasos retinianos, palidez de disco e aumento de escavação em olho esquerdo. Ao exame da biomicroscopia ultrassônica, foi evidenciado corpo ciliar anteriorizado e ausência de sulco ciliar em ambos os olhos, relevando presença de íris em plateau. Ao exame de tomografia de coerência óptica, visualizamos presença de edema macular cistoide bilateral. O screening genético revelou heterozigose no gene CRB1 (c.2843G>A and c.2506C>A), confirmando o diagnóstico de retinose pigmentar. Este caso reforça a importância do exame de gonioscopia e da avaliação da pressão intraocular em pacientes em câmara rasa, mesmo em pacientes jovens. Além disso, mostra a importância do screening genético como ferramenta útil para elucidação diagnóstica.

Analysis of a patient with early-onset retinitis pigmentosa due to novel variants of CRB1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a patient with early-onset retinitis pigmentosa (RP).@*METHODS@#A patient who had presented at the West China Hospital of Sichuan University on March 10, 2020 was selected as the study subject. The patient and his parents were subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and in silico analysis.@*RESULTS@#The patient has featured substantial loss of binocular vision field. Funduscopy revealed characteristic bone spicule-type pigment deposits, as well as attenuated retinal arterioles and pale-appearing optic discs. WES revealed that he has harbored compound missense variants of a RP-associated CRB1 gene, including c.2969T>C (p.Leu990Ser) and c.1816T>C (p.Cys606Arg), which were respectively inherited from his father and mother. Homozygous c.1816T>C (p.Cys606Arg) variant has been identified among RP patients, whilst the c.2969T>C (p.Leu990Ser) variant was unreported previously. Both variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).@*CONCLUSION@#The novel compound heterozygous variants of the CRB1 gene probably underlay the early-onset RP in this patient. Above finding has enriched the mutational spectrum of the CRB1 gene.

Analysis of RS1 gene variant in a Chinese pedigree affected with X-linked congenital retinal splitters / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with X-linked retinoschisis.@*METHODS@#Clinical data of the pedigree was collected. Following DNA extraction, PCR and Sanger sequencing were carried out to detect potential variant in the RS1 gene. The result was verified by using PCR and restriction fragment length polymorphism assay.@*RESULTS@#All male patients were found to harbor a c.458T>G (p.Val153Gly) variant of the RS1 gene, for which Their mothers were heterozygous carriers. The same variant was not detected among unaffected members of the pedigree as well as 100 healthy controls. Bioinformatic analysis suggested the variant to be pathogenic.@*CONCLUSION@#The c.458T>G (p.Val153Gly) variant of the RS1 gene probably underlay the X-linked retinoschisis in this pedigree.

Retinosquisis ligada al cromosoma X: presentación de un caso clínico y análisis del diagnóstico genético / X-linked Retinoschisis: a case report and genetic diagnosis analysis / Retinosquise ligada ao X: a presentação de um caso clínico e análise do diagnóstico genético

La Retinosquisis ligada al X, que se presenta fundamentalmente en varones, es una enfermedad genética caracterizada por agudeza visual reducida debido a degeneración macular. Su prevalencia es de 1/5000 varones en todo el mundo. Se manifiesta desde la primera década de la vida con pérdida de la visión que progresa hasta la adolescencia y se mantiene estable hasta la 4ta década de la vida, momento en que presenta un declive importante. El fondo de ojo suele mostrar esquisis. Las mujeres portadoras rara vez presentan síntomas. El gen involucrado es RS1, codifica para Retinosquina, proteína que participa en la integridad estructural y funcional de la retina. El mismo presenta diferentes mutaciones que generan pérdida de función de la proteína. La sospecha diagnóstica se basa en la clínica y los antecedentes familiares, y se apoya en la paraclínica confirmándose en la mayoría de los casos mediante secuenciación del gen. El tratamiento consiste en control periódico oftalmológico y cirugía de las complicaciones. Presentamos el caso de un niño de 2 años con episodios reiterados de desprendimiento de retina, con antecedentes familiares de Retinosquisis por línea materna en individuos de sexo masculino. Estos fueron estudiados demostrándose que son portadores de la variante probablemente patogénica c.466A>C (Arg156Gly) en el gen RS1 la cual había sido reportada previamente en una familia de origen chino. Se demostró que nuestro paciente presenta la mutación familiar en hemicigosis, por lo que esta es la segunda familia en que se confirma la segregación de esta variante con Retinosquisis.

X-linked Retinoschisis is a genetic disease characterized by reduced visual acuity mainly in men due to juvenile macular degeneration. Its prevalence is 1/5000 men worldwide. It manifests from the first decade of life with loss of vision that progresses to adolescence and then remains stable until the 4th decade of life, when it may present a significant decline. The fundus exam usually shows schism. Carrier women rarely have symptoms. The gene involved is RS1 (Xp22.13), which encodes for Retinoschisin, a protein that participates in the structural and functional integrity of the retina. In affected cases, mutations that generate loss of protein function were demonstrated. The diagnosis is based on the clinical and family history, and is supported by ophthalmology evaluation; in most cases it can be confirmed by sequencing of the gene. The treatment consists of periodic ophthalmological control and surgery of the complications. We describe the case of a 2 year old boy with repeated episodes of retinal detachment and who has a family history of Retinoschisis by maternal line in male individuals. These were studied, and it was shown that they are carriers of the probably pathogenic variant c.466A> C (Arg156Gly) in the RS1 gene, which had been reported previously in a family of Chinese origin. It was shown that our patient presents the family mutation in hemizygous state, so this is the second family in which the segregation of this variant with Retinoschisis is confirmed.

A retinosquise ligada ao X, que ocorre principalmente em homens, é uma doença genética caracterizada pela redução da acuidade visual devido à degeneração macular. Sua prevalência é de 1/5000 homens em todo o mundo. Manifesta-se desde a primeira década de vida com perda da visão que progride até a adolescência e permanece estável até a 4ª década de vida, época em que apresenta declínio significativo. O fundo geralmente mostra esquise. Portadoras do sexo feminino raramente apresentam sintomas. O gene envolvido é o RS1, que codifica a Retinosquina, proteína que participa da integridade estrutural e funcional da retina. Apresenta diferentes mutações que geram perda de função da proteína. A suspeita diagnóstica baseia-se na história clínica e familiar, e na paraclínica, sendo confirmada na maioria dos casos pelo sequenciamento gênico. O tratamento consiste em acompanhamento oftalmológico periódico e cirurgia para complicações. Apresentamos o caso de um menino de 2 anos com episódios repetidos de descolamento de retina, com história familiar de retinosquise materna no sexo masculino. Estes foram estudados mostrando que são portadores da variante provavelmente patogênica c.466A> C (Arg156Gly) no gene RS1, que havia sido relatado anteriormente em uma família de origem chinesa. Foi demonstrado que nosso paciente apresenta a mutação familiar em hemizigose, sendo esta a segunda família em que se confirma a segregação desta variante com Retinosquise.

Methylation status of DACH1 gene in esophageal cancer and its clinical significance / 中华医学遗传学杂志

OBJECTIVE@#To analyze the correlation of methylation status of dachshund homolog 1 (DACH1) gene in tumor tissues with clinicopathological characteristics and prognosis of patients of esophageal cancer.@*METHODS@#Tumor tissue, paracancerous tissue and normal esophageal mucosal specimens of 104 patients with esophageal cancer were collected. Methylation-specific PCR was used to determine the methylation status of the DACH1 gene. Univariate analysis and multivariate Logistic regression model were used to analyze the correlation between DACH1 methylation status and clinical pathological characteristics of the patients. Kaplan-Meier survival curve was used to analyze the relationship between DACH1 methylation status and prognostic survival of patients.@*RESULTS@#The methylation rate of the DACH1 gene in esophageal cancer tumor tissue was 30.77% (32/104), which was higher than those in adjacent tissues (1.92%) and normal esophageal mucosa (0%) (P 0.05) but tumor differentiation, TNM staging, and lymph node metastasis(P< 0.05). The degree of tumor differentiation, TNM stage, and lymph node metastasis of patients are independent risk factors for the methylation status of the DACH1 gene. By March 2020, 89 of the 104 patients had died. Among them, the median survival foresophageal cancer patients with DACH1 gene methylation was 22 months, which was lower than 34 months of those without DACH1 methylation (P< 0.05).@*CONCLUSION@#Methylation of the DACH1 gene may be involved in the occurrence and progress of esophageal cancer. The degree of tumor differentiation, TNM stage, and lymph node metastasis of patients are independent risk factors for the methylation status of the DACH1 gene. Patients with esophageal cancer but unmethylated DACH1 gene have a longer prognostic survival.

Osteogenesis Imperfecta Type VI with Severe Bony Deformities Caused by Novel Compound Heterozygous Mutations in SERPINF1

Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by bone fragility, frequent fractures, and low bone mass. Dominantly inherited COL1A1 or COL1A2 mutations appear to be causative in the majority of OI types, but rare recessively inherited genes have also been reported. Recently, SERPINF1 has been reported as another causative gene in OI type VI. To date, only eight SERPINF1 mutations have been reported and all are homozygous. Our patient showed no abnormalities at birth, frequent fractures, osteopenia, and poor response on pamidronate therapy. At the time of her most recent evaluation, she was 8 yr old, and could not walk independently due to frequent lower-extremity fractures, resulting in severe deformity. No clinical signs were seen of hearing impairment, blue sclera, or dentinogenesis imperfecta. In this study, we describe the clinical and radiological findings of one Korean patient with novel compound heterozygous mutations (c.77dupC and c.421dupC) of SERPINF1.

The expression of melanopsin and clock genes in Xenopus laevis melanophores and their modulation by melatonin

Vertebrates have a central clock and also several peripheral clocks. Light responses might result from the integration of light signals by these clocks. The dermal melanophores of Xenopus laevis have a photoreceptor molecule denominated melanopsin (OPN4x). The mechanisms of the circadian clock involve positive and negative feedback. We hypothesize that these dermal melanophores also present peripheral clock characteristics. Using quantitative PCR, we analyzed the pattern of temporal expression of Opn4x and the clock genes Per1, Per2, Bmal1, and Clock in these cells, subjected to a 14-h light:10-h dark (14L:10D) regime or constant darkness (DD). Also, in view of the physiological role of melatonin in the dermal melanophores of X. laevis, we determined whether melatonin modulates the expression of these clock genes. These genes show a time-dependent expression pattern when these cells are exposed to 14L:10D, which differs from the pattern observed under DD. Cells kept in DD for 5 days exhibited overall increased mRNA expression for Opn4x and Clock, and a lower expression for Per1, Per2, and Bmal1. When the cells were kept in DD for 5 days and treated with melatonin for 1 h, 24 h before extraction, the mRNA levels tended to decrease for Opn4x and Clock, did not change for Bmal1, and increased for Per1 and Per2 at different Zeitgeber times (ZT). Although these data are limited to one-day data collection, and therefore preliminary, we suggest that the dermal melanophores of X. laevis might have some characteristics of a peripheral clock, and that melatonin modulates, to a certain extent, melanopsin and clock gene expression.

A Case of 9.7 Mb Terminal Xp Deletion Including OA1 Locus Associated with Contiguous Gene Syndrome

Terminal or interstitial deletions of Xp (Xp22.2-->Xpter) in males have been recognized as a cause of contiguous gene syndromes showing variable association of apparently unrelated clinical manifestations such as Leri-Weill dyschondrosteosis (SHOX), chondrodysplasia punctata (CDPX1), mental retardation (NLGN4), ichthyosis (STS), Kallmann syndrome (KAL1), and ocular albinism (GPR143). Here we present a case of a 13.5 yr old boy and sister with a same terminal deletion of Xp22.2 resulting in the absence of genes from the telomere of Xp to GPR143 of Xp22. The boy manifested the findings of all of the disorders mentioned above. We began a testosterone enanthate monthly replacement therapy. His sister, 11 yr old, manifested only Leri-Weill dyschondrosteosis, and had engaged in growth hormone therapy for 3 yr. To the best of our knowledge, this is the first report of a male with a 9.7 Mb terminal Xp deletion including the OA1 locus in Korea.

The genetic and molecular basis of congenital cataract / Base genética e molecular da catarata congênita

Congenital cataracts are one of the most treatable causes of visual impairment and blindness during infancy, with an estimated prevalence of 1 to 6 cases per 10,000 live births. Approximately fifty percent of all congenital cataract cases may have a genetic cause. All three types of Mendelian inheritance have been reported for cataract; however, autosomal dominant transmission seems to be the most frequent. The transparency and high refractive index of the lens are achieved by the precise architecture of the fiber cells and the homeostasis of the lens proteins in terms of their concentration, stability, and supramolecular organization. Research on hereditary congenital cataract led to the identification of several classes of candidate genes that encode proteins such crystallins, lens specific connexins, aquaporine, cytoskeletal structural proteins, and developmental regulators. The purpose of this study was to review the literature on the recent advances made in understanding the molecular genetic basis of congenital cataracts.

A catarata congênita é uma das principais causas tratáveis de cegueira na infância, com prevalência estimada em 1 a 6 casos por 10.000 nascidos vivos, sendo a causa hereditária responsável por até metade dos casos. Dentre os padrões de herança já descritos para a catarata, a transmissão autossômica dominante é a mais frequente. A transparência e o alto índice refrativo do cristalino são resultados da disposição regular das fibras lenticulares e do equilíbrio homeostático; além da estabilidade e da organização supramolecular das proteínas do cristalino. Pesquisas sobre catarata congênita hereditária têm levado à identificação de várias classes de genes responsáveis pela codificação das proteínas do cristalino, tais como: cristalinas, conexinas, aquaporinas, proteínas do citoesqueleto e reguladores do desenvolvimento. O objetivo deste estudo foi a revisão da literatura sobre os recentes avanços na compreensão da base genética e molecular da catarata congênita.

Complex genetic mechanisms in glaucoma: An overview.

Glaucomas comprise a group of hereditary optic neuropathies characterized by progressive and irreversible visual field loss and damage to the optic nerve head. It is a complex disease with multiple molecular mechanisms underlying its pathogenesis. Genetic heterogeneity is the hallmark of all glaucomas and multiple chromosomal loci have been linked to the disease, but only a few genes have been characterized, viz. myocilin (MYOC), optineurin (OPTN), WDR36 and neurotrophin-4 (NTF4) in primary open angle glaucoma (POAG) and CYP1B1 and LTBP2 in congenital and developmental glaucomas. Case-control-based association studies on candidate genes involved in different stages of glaucoma pathophysiology have indicated a very limited involvement. The complex mechanisms leading to glaucoma pathogenesis indicate that it could be attributed to multiple genes with varying magnitudes of effect. In this review, we provide an appraisal of the various efforts in unraveling the molecular mystery in glaucoma and also some future directions based on the available scientific knowledge and technological developments.

Absence of mutations in Pax6 gene in three cases of Morning Glory syndrome associated with isolated growth hormone deficiency / A ausência de mutações no gene PAX6 em três casos de síndrome de Morning Glory associada à deficiência isolada de hormônio do crescimento

Morning glory syndrome (MGS) is a congenital optic disc dysplasia often associated with craniofacial anomalies, especially basal encephalocele and hypopituitarism. Clinical signs are varied and often occult. The PAX6 gene is involved in ocular morphogenesis and is expressed in numerous ocular tissues during development especially in the developing central nervous system. The aim of the present study is to evaluate PAX6 in MGS associated with isolated growth hormone deficiency. Three pre-pubertal males (A, B and C) with MGS and short stature due to growth hormone deficiency, treated with recombinant human growth hormone with limited response, were reported. Two of them had basal encephalocele. Coding and non-coding sequences corresponding of PAX6 different transcripts were analyzed by direct sequencing. Nucleotide variations causing putative aminoacid change were not observed. Patient A presented the new IVS2+9G>A transition, whereas patients A and C were heterozygous for known single nucleotide polymorphisms (SNP) within the intron 4. In addition, two SNP heterozygoses were observed for patient C in both intron 9 and 13. Sequencing also revealed several nucleotide variations in patient B. Two heterozygoses for known polymorphisms were identified along with a novel C>A nucleotide change in intron 4. This patient also presented a low number on the TG repeat in intron 9 and a new IVS11+33A>T transversion. Gene regulation and transcription of PAX6 are complex processes; there are two major protein isoforms, PAX6(-5a) and PAX6(+5a), and nine transcripts described. Furthermore, extra transcription regulatory elements have been postulated within PAX6 introns. Considering that neither population distributions on PAX6 polymorphism nor their linkeages with diseases have been reported, a functional effect due to alterations described here cannot be discarded.

A síndrome de Morning Glory (SMG) é uma displasia óptica congênita associada a anomalias craniofaciais, principalmente encefalocele basal e hipopituitarismo. Os sinais clínicos são variados e muitas vezes ocultos. O gene PAX6 está envolvido na morfogênese ocular e se expressa em vários tecidos oculares durante o desenvolvimento do sistema nervoso central. O objetivo deste estudo foi avaliar o gene PAX6 na SMG associada com deficiência isolada de hormônio de crescimento. Foram relatados três pacientes pré-púberes (A, B e C) com SMG e baixa estatura por deficiência de hormônio de crescimento tratados com hormônio de crescimento recombinante humano. As seqüências codificadoras e não-codificadoras correspondentes ao PAX6 em diferentes transcritos foram analisadas por seqüenciamento direto. Variações nucleotídeas com trocas pontuais de aminoácidos não foram encontradas. O paciente A apresentou uma transição nova IVS2+9G>A, enquanto os pacientes A e C foram heterozigotos para um polimorfismo (SNP) no íntron 4. Ainda, dois SNPs em heterozigose nos íntrons 9 e 13 foram observados no paciente C. O seqüenciamento também mostrou várias variações nucleotídeas no paciente B. Dois SNPs conhecidos com a alteração nucleotídea nova C>A no íntron 4 foram observados em heterozigose. Este paciente também apresentou um baixo número de repetições TG no íntron 9 e uma nova transversão IVS11+33A>T. A regulação e a transcrição do gene PAX6 são um processo complexo; existem 2 isoformas principais da proteína, PAX6(-5a) e PAX6(+5a) e 9 transcritos descritos. Considerando que nem a distribuição de SNPs no PAX6 e nem as suas ligações com as doenças foram relatadas, um defeito funcional devido às alterações descritas não pode ser descartado.

WAGR syndrome--a case report.

The WAGR syndrome is a multiple congenital anomaly-mental retardation syndrome caused by interstitial deletion of the distal portion of chromosome 11p13. It is a contiguous gene deletion syndrome, and WAGR is an acronym for the primary features: W for Wilms tumor, A for aniridia, G for genital anomalies, and R for mental retardation. Wilms tumor and male genital anomalies are caused by deletion of the WT1 tumor-suppressor gene, and aniridia is caused by deletion of PAX6 ocular developmental gene. Mental retardation is presumed to be a consequence of deletion of multiple as yet unidentified genes in the region. Individuals with the WAGR syndrome have a high risk for developing Wilms tumor and late-onset renal failure, and should be monitored for these complications.

Mutation analysis of gene PAX6 in human gliomas

Gliomas are the most common tumors of the central nervous system. In spite of the marked advances in the characterization of the molecular pathogenesis of gliomas, these tumors remain incurable and, in most of the cases, resistant to treatments, due to their molecular heterogeneity. Gene PAX6, which encodes a transcription factor that plays an important role in the development of the central nervous system, was recently recognized as a tumor suppressor in gliomas. The objective of the present study was to analyze the mutational status of the coding and regulating regions of PAX6 in 94 gliomas: 81 astrocytomas (11 grade I, 23 grade II, 8 grade III, and 39 grade IV glioblastomas), 5 oligodendrogliomas (3 grade II, and 2 grade III), and 8 ependymomas (5 grade II, and 3 grade III). Two regulating regions (SX250 and EIE) and the 11 coding regions (exons 4-13, plus exon 5a resulting from alternative splicing) of gene PAX6 were analyzed and no mutation was found. Therefore, we conclude that the tumor suppressor role of PAX6, reported in previous studies on gliomas, is not due to mutation in its coding and regulating regions, suggesting the involvement of epigenetic mechanisms in the silencing of PAX6 in these tumors.

Correlation between genotype and phenotype in primary open angle glaucoma of Brazilian families with mutations in exon 3 of the TIGR/MYOC gene

OBJETIVO: Identificar nos representantes de famílias com glaucoma primário de ângulo aberto (GPAA) mutações no exon 3 do gene TIGR/MYOC e avaliar a expressão fenotípica associada às mutações encontradas em seus respectivos núcleos familiares. MÉTODOS: Setenta e oito pacientes (81,2%), com pelo menos um representante na família com GPAA, e dezoito pacientes (18,7%) com glaucoma esporádico tiveram o exon 3, do gene TIGR/MYOC, submetido a seqüenciamento automático para identificação de mutações. Os pacientes, com mutação não silenciosa identificadas nesta triagem inicial, tiveram os heredogramas de suas famílias construídos. Todos os seus familiares disponíveis foram submetidos a exame oftalmológico e seqüenciamento automático do exon 3, do gene TIGR/MYOC.RESULTADOS: Foram identificados quatro tipos de variações na seqüência do exon 3 do TIGR/MYOC (Cys433Arg, Pro370Pro, Lys398Arg e Tyr347Tyr) nos 96 pacientes inicialmente estudados. A mutação Lys398Arg previamente descrita como polimorfismo não segregou com a doença na família estudada. A mutação Cys433Arg foi a mais prevalente afetando 3,1% da amostra inicial (3/96). Em duas diferentes famílias (56 integrantes disponíveis para exame), 8/56 carregavam a mutação Cys433Arg e tinham GPAA, 5/56 com mutação eram hipertensos oculares e 8/56 com mutação não apresentavam manifestações da doença. Pacientes com GPAA apresentaram mediana de idade de diagnóstico de 43,25 anos, variando entre 17-58, e média de pressão intra-ocular (PIO) de 36,3±3,8 mmHg para olho direito e 37,6±9,75 mmHg para olho esquerdo. O grupo com a mutação Cys433Arg apresentou PIO significantemente mais elevada (p<0,0007) e relação escavação/disco vertical mais comprometida (p<0,023) que o grupo de pacientes sem mutação.CONCLUSÃO: A mutação no exon 3 do gene TIGR/MYOC associa-se com famílias brasileiras portadoras de GPAA de início precoce. O fenótipo desta mutação é caracterizado por variável idade de diagnóstico, causando GPAA-juvenil e GPAA do adulto, PIO bastante elevada, de difícil controle, freqüentemente levando a grave comprometimento visual.

A Novel Mutation in the XLRS1 Gene in a Korean Family with X-linked Retinoschisis

PURPOSE: To report a novel missense mutation in the XLRS1 gene in a Korean family with X-linked retinoschisis. METHODS: Observation case report of a family with a proband with X-linked retinoschisis underwent complete ophthalmologic examination. Genomic DNA was excluded from the family's blood and all exons of the XLRS1 gene were amplified by polymerase chain reaction and analyzed using a direct sequencing method. RESULTS: A novel Leu103Phe missense mutation was identified. CONCLUSIONS: A novel Leu103Phe mutation is an additional missense mutation which is responsible for the pathogenesis of X-linked retinoschisis.

Genetics and bioinformatics of primary open angle glaucoma: an Indian perspective.

Glaucoma is the second largest blinding disorder, after cataract, affecting about 67 million people worldwide. In India about 1.5 million people are blind due to glaucoma. Primary open angle glaucoma is the major sub-type of glaucoma affecting all ages and is genetically complex. Myocilin and optineurin are two different genes that have been implicated for primary open angle glaucoma. This review is focused on the studies being conducted in India on primary open angle glaucoma to identify the molecular defects and new directions undertaken using bioinformatic approaches towards a better understanding of the disease.

Glaucoma in Costa Rica. Initial approaches: [minireview]

Glaucoma is the second most frequent cause of irreversible blindness worldwide. Genetic factors have been implicated in the development of the disease. So far six loci (GLC1A-GLC1F) and two genes (TIGR/MYOC and OPTN) are involved in the development of juvenile (JOAG) and adult onset or chronic primary open angle glaucoma (COAG), while two loci (GLC3A,GLC3B) and one gene (CYP1B1) are known for primary congenital glaucoma (PCG). Here we summarize the results of the first genetic studies of glaucoma in Costa Rica. Nine families: 1 with JOAG, 1 with PCG and 7 with COAG were screened for mutations at the known genes. A 10 bp duplication, 1546-1555dupTCATGCCACC, at the CYP1B1 gene, causes, in homozygous state, glaucoma in the consanguineous PCG family. This mutation has been found in different countries and generates an early stop codon that termitates protein synthesis 140 amino acids earlier than the normal allele. In exon 1 of the T1GR/MYOC the innocuous Arg76Lys variant was found in two of the COAG families. In the OPTN gene two variants in the coding region (Thr34Thr, Met 98Lys) and 7 intronic changes were found in other Costa Rican glaucoma patients. One of the COAG families was chosen for a genome scan with 379 microsatellite markers and linkage analysis. LOD scores [quot ]suggestive[quot ] of linkage were obtained for several chromosomal regions. Evidence indicates that hereditary glaucoma in Costa Rica is highly heterogeneous and that further studies in the country will probably disclose some up to now unknown genes responsible for the disease.

Mutations of the Norrie gene in Korean ROP infants

The present study was conducted to evaluate if there is a Norrie disease gene (ND gene) mutation involved in the retinopathy of prematurity (ROP), and to identify the possibility of a genetic abnormality that may be linked to the presence of ROP. Nineteen premature Korean infants, with a low birth weight (1500 g or less) or low gestational age (32 weeks or less), were included in the study. Eighteen infants had ROP, and the other did not. Genomic DNA was isolated from the peripheral blood leukocytes of these patients, and all three exons and their flanking areas, all known ND gene mutations regions, were evaluated following amplification by a polymerase chain reaction, but no ND gene mutations were detected. Any disagreement between the relationship of ROP to the ND gene mutation will need to be clarified by further investigation.