Genetic diagnosis of 3 families with choroideremia / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical manifestations and causative gene variants of the choroideremia patients, and to help the patients bedifferential diagnosed by whole exome sequencing and provide theoretical basis for their genetic counseling.@*METHODS@#Clinical data of 3 families were collected and genomic DNA was extracted respectively from peripheral blood of patients and related subjects. Exome targeted sequencing was used to screen suspicious gene mutations. Sanger sequencing and quantitative PCR were used to verify the candidate mutations and investigate the mutation carrying status of other members of the family. The candidate mutations were searched through HGMD and PubMed databases for the pathogenicity reports, and the pathogenicity of candidate mutations was judged according to a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.@*RESULTS@#The proband of family 1 is c.1584_1587del (p.Val529Hisfs*6) variant hemizygote, whose daughter carries c.1584_1587del (p.Val529Hisfs*6) heterozygous variation. The proband of family 2 is a hemizygote with deletion of exons 10 to 15 (E10-15del), and her mother and sister carry the E10-15del heterozygous variation. In family 3, the proband is c.544delT (p.Cys182Valfs*14) variant hemizygote, and his mother is c.544delT (p.Cys182Valfs*14) heterozygote, but the father do not detect this variant. All the 3 families were detected pathogenic gene variations of CHM, two of which were known pathogenic variation and one of which was novel CHM gene c.544delT (p.C182Vfs*14) in this study. The c.544delT frameshift mutation of CHM gene can lead to the premature termination of the product protein translation and nonfunctioning protein. It is a pathogenic mutation according to ACMG guidelines.@*CONCLUSION@#The findings of this study expand the gene variation spectrum of choroideremia.

Coroideremia familiar: reporte de caso con énfasis en la evolución clínica y adquisición de discapacidad visual / Familiar choroideremia: case report with emphasis on clinical evolution and acquisition of visual impairment

Resumen La coroideremia es una enfermedad retiniana hereditaria que se caracteriza por la degeneración progresiva coriocapilar de coroides y retina; esta tiene la capacidad de limitar el funcionamiento y generar discapacidad, afectando el desempeño de la persona en el ámbito familiar, social y profesional, al producir dificultades en la comunicación, la movilidad, el desplazamiento y la gestión de su diario vivir. Esta condición de salud ocular se origina por una mutación del gen que codifica la proteína RabEscort-1, ubicada en el cromosoma Xq21. Su fisiopatología no es clara, y los reportes de caso de coroideremia familiar son escasos en Latinoamérica. Se reporta el caso de un hombre de 54 años con nictalopía y pérdida progresiva de agudeza visual, con un hermano menor con coroideremia y primo materno con sospecha de dicha enfermedad, con énfasis en evolución clínica, hallazgos al fondo de ojo y progresión a discapacidad categoría visual, tipo baja visión. MÉD.UIS. 2020;33(2):109-115.

Abstract Choroideremia is a hereditary retinal disease characterized by progressive choroidal and retinal choriocapillary degeneration, it has the ability to limit functioning and generate disability, affecting the persons performance in the family, social and professional environment, by causing difficulties in communication, mobility, displacement and management of your daily life. This eye health condition is caused by a mutation of the gene that encodes the RabEscort-1 protein, located on the Xq21 chromosome. His pathophysiology is not clear, and case reports of familial choroideremia are sparse in Latin America. The case of a 54-year-old man with night blindness and progressive loss of visual acuity is reported, with a younger brother with choroideremia and maternal cousin with suspected disease, with emphasis on clinical evolution, fundus findings and progression to disability category visual, low vision type. MÉD.UIS. 2020;33(2):109-115.

Genetic Mutation Profiles in Korean Patients with Inherited Retinal Diseases

BACKGROUND: Because of genetically and phenotypically heterogenous features, identification of causative genes for inherited retinal diseases (IRD) is essential for diagnosis and treatment in coming gene therapy era. To date, there are no large-scale data of the genes responsible for IRD in Korea. The aim of this study was to identify the distribution of genetic defects in IRD patients in Korea. METHODS: Medical records and DNA samples from 86 clinically diagnosed IRD patients were consecutively collected between July 2011 and May 2015. We applied the next-generation sequencing strategy (gene panel) for screening 204 known pathogenic genes associated with IRD. RESULTS: Molecular diagnoses were made in 38/86 (44.2%) IRD patients: 18/44 (40.9%) retinitis pigmentosa (RP), 8/22 (36.4%) cone dystrophy, 6/7 (85.7%) Stargardt disease, 1/1 (100%) Best disease, 1/1 (100%) Bardet-Biedl syndrome, 1/1 (100%) congenital stationary night blindness, 1/1 (100%) choroideremia, and 2/8 (25%) other macular dystrophies. ABCA4 was the most common causative gene associated with IRD and was responsible for causing Stargardt disease (n = 6), RP (n = 1), and cone dystrophy (n = 1). In particular, mutations in EYS were found in 4 of 14 autosomal recessive RP (29%). All cases of Stargardt disease had a mutation in the ABCA4 gene with an autosomal recessive trait. CONCLUSION: This study provided the distribution of genetic mutations responsible for causing IRD in the Korean patients. This data will serve as a reference for future genetic screening and treatment for Korean IRD patients.

Identification of Pathogenic Variants in the CHM Gene in Two Korean Patients With Choroideremia

Choroideremia is a rare X-linked disorder causing progressive chorioretinal atrophy. Affected patients develop night blindness with progressive peripheral vision loss and eventual blindness. Herein, we report two Korean families with choroideremia. Multimodal imaging studies showed that the probands had progressive loss of visual field with characteristic chorioretinal atrophy, while electroretinography demonstrated nearly extinguished cone and rod responses compatible with choroideremia. Sanger sequencing of all coding exons and flanking intronic regions of the CHM gene revealed a novel small deletion at a splice site (c.184_189+3delTACCAGGTA) in one patient and a deletion of the entire exon 9 in the other. This is the first report on a molecular genetic diagnosis of choroideremia in Korean individuals. Molecular diagnosis of choroideremia should be widely adopted for proper diagnosis and the development of new treatment modalities including gene therapy.

Regression of Choroidal Neovascularization in a Choroideremia Patient after Intravitreal Bevacizumab Injection: A Case Report

PURPOSE: To report the first domestic case of choroidal neovascularization in a choroideremia patient treated with intravitreal bevacizumab injection. CASE SUMMARY: A 29-year-old male presented with a sudden decline in vision in the left eye. Fundus examination revealed areas of choriocapillaries and retinal pigment epithelium atrophy with macular hemorrhage. Fluorescein angiogram revealed vascular hyperfluorescence in the juxtafoveal area. Neurosensory detachment around the macula and increased central macular thickness was also observed using optical coherence tomography. Upon the diagnosis of choroideremia with choroidal neovascularization, the patient was treated with 1.25 mg intravitreal bevacizumab. Visual acuity improved after four injections of intravitreal Bevacizumab with improvement in both detachment and fluorescein leakage. CONCLUSIONS: In patients with choroideremia presenting sudden decline in vision, ophthalmologists should detect for possible choroidal neovascularization. The results from the present study show that judicious use of intravitreal Bevacizumab may be effective in such cases. Further studies with a large sample size and sufficiently long follow-up periods are required.

Classificação diagnóstica dos portadores de doenças degenerativas de retina, integrantes dos grupos Retina São Paulo e Retina Vale do Paraíba / Diagnostic classification of retinal degenerative diseases São Paulo and Vale Retina groups

OBJETIVO:Organizar um banco de dados regional de todos os indivíduos portadores de doenças degenerativas da retina, com o objetivo de classificar cada paciente de acordo com o tipo de distrofia e padräo de herança. MÉTODOS: Durante o encontro do Grupo Retina Säo Paulo no dia 5 de maio de 2001, duzentas e quarenta e três pessoas foram registradas, sendo que parte forneceu dados de antecedentes oculares, pessoais e familiares e árvore genealógica. Noventa e três pacientes foram questionados quanto a idade, origem, tipo de distrofia, história familiar e árvore genealógica, tipo de herança, outras anomalias sistêmicas e exames complementares. Foram classificados quanto ao diagnóstico e padrão de herança. RESULTADOS: Dos duzentos e quarenta e três pacientes registrados, as distrofias encontradas foram retinose pigmentária, doença de Stargardt, síndrome de Usher, amaurose congênita de Leber e coroideremia. Quanto à divisäo por doença dos 93 pacientes argüidos, havia 62 pacientes com retinose pigmentária, 13 com doença de Stargardt, 13 com síndrome de Usher, três com amaurose congênita de Leber e dois com coroideremia. Dos pacientes com retinose pigmentária, o padräo de herança detectado foi autossômico dominante em quatro casos (7 por cento), autossômico recessivo em vinte casos (32 por cento), ligado ao cromossomo X recessivo em sete casos (11 por cento), caso isolado em vinte e nove (47 por cento) e padräo indeterminado em dois (3 por cento). Para a doença de Stargardt três indivíduos (23 por cento) seguiam o padräo de herança autossômico recessivo e dez (77 por cento) eram casos isolados. Dos treze pacientes com síndrome de Usher, oito (61,5 por cento) apresentavam herança autossômica recessiva, quatro (31 por cento) eram casos isolados e um (7,5 por cento) tinha o padräo de herança indeterminado. Os dois pacientes com coroideremia seguiam o padräo de herança ligado ao X recessivo. Para amaurose congênita de Leber, um paciente (33,5 por cento) tinha padräo autossômico recessivo de herança e dois (66,5 por cento) eram casos isolados. CONCLUSÄO: Destaca-se assim a importância desta classificaçäo como a primeira referência nacional dos padrões de hereditariedade das distrofias retinianas do país. Este é o primeiro passo para se proceder em seguida a classificação genético-molecular baseada no seqüenciamento de cada gene responsável por cada um dos padrões de herança. A freqüência de cada tipo específico é semelhante à encontrada em outros trabalhos...

Atrofia girata de coróide e retina: relato de caso / Girate atrophy of the retina and choroid: case report

OBJETIVO: Relatar um caso de atrofia girata de coróide e retina com confirmação por meio da bioquímica do plasma. MÉTODO: Aferiu-se a melhor acuidade visual corrigida de ambos olhos (AO) em tabela de Snellen. Foram realizados biomicroscopia do segmento anterior, refração, mapeamento de retina, angiografia fluoresceínica, campo visual e dosagem da ornitina sérica (aminoacidograma). RESULTADOS: Paciente de 22 anos, sexo feminino, cor branca, apresentando alta miopia e acuidade visual (AV) 20/100 em AO. A biomicroscopia do segmento anterior apresentava catarata subcapsular posterior em AO. A oftalmoscopia foram verificadas lesöes atróficas da coróide e da retina bem delimitadas em meia periferia de AO. O aminoacidograma constatou elevaçäo correspondente ao complexo da ornitina. CONCLUSÃO: Relata-se um caso típico de atrofia girata, distrofia retiniana rara associada a hiperornitinemia

A Case of Choroideremia with Recurrent Anterior Uveitis

Choroideremia is a rare hereditary disease with characteristic fundus that causes night blindness and peripheral visual field loss. The authors encounter choroideremia accompanied by recurrent uveitis. This paper is designed to give a description of the condition, along with an investigation of the literature. Ophthalmological tests and treatments were performed. Characteristic fundus, night blindness, peripheral visual field loss, electroretinography and other manifestations led us to a diagnosis of choroideremia. The anterior uveitis was managed with medication.

Coroideremia: Formas e características clínicas / Choroideremia clinical aspects and forms of presentation

Trata-se do estudo de 15 pessoas de uma mesma família, com oito casos de coroideremia, dos quais quatro são pacientes doentes, quatro são pacientes portadores, quatro são normais. Três não foram estudados. Através desse relato enfatizamos a herança recessiva ligada ao sexo e seu caráter progressivo, bem como a variedade de achados clínicos que acompanham as diversas modalidades de apresentação da doença. Tendo em vista a inexistência de tratamento clínico comprovado cientificamente, os pacientes foram encaminhados para aconselhamento genético e orientados quanto à necessidade de proteção ocular da luz.

Atrofia girata de coróide e retina / Gyrate atrophy of choroid and retina

Os autores tecem comentários a respeito da atrofia girata da coróide e retina, com ênfase para os distúrbios genéticos e metabólicos como a hiperornitinemia. Apresentam um caso bastante avançado e discutem as possibilidades terapêuticas com doses elevadas de piridoxina

Clinical features of choroideremia in a 5-generation pedigree

This report describes the clinical and morphological features of X-linked recessive chorioretinal disorder called Choroideremia in five generations of one family. The pedigree shows the typical X-linked transmission. The fundus changes of carrier state, [salt and pepper] appearance of the ocular fundus, in one female twin of 25 and midperipheral pigmentation in the other, the typical appearance of Choroideremia in two affected males of 53 and 54, and a beginning stage in a 4-year-old boy were found. This study demonstrates that due to the uncharacteristic features in the early stages of the disease in the afflicted males and the carrier state fundus changes that might not appear clinically important, the examination of family members is essential for accurate diagnosis and proper medical management of choroideremia

Choroideremia

Choroideremia is characterized by progressive atrophy of choroid and pigment epithelium of retina leading to night blindness and gross loss of field. and is inherited as X chromosome linked intermediate. Authors experienced 2 cases among a family of choroideremia. The clinical finding and brief reviews of literatures are reported as followings.