RESUMO
AIM: This study reports the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins subsequently diagnosed with Wilms tumour (WAGR syndrome). METHODS: Two monozygotic female twins were referred at age 2 months with bilateral corneal opacity. A diagnosis of Peters' anomaly associated to aniridia was made in both eyes of both twins. Physical examination and ultrasonography were carried out at 12 months of age to explore the possibility of WAGR-related anomalies, specifically Wilms tumour. DNA were isolated and subjected to whole exome sequencing. RESULTS: Peters' anomaly associated to aniridia in both eyes as well as bilateral Wilms tumour in both children were diagnosed. Exome analyses showed a large heterozygous deletion encompassing 6 648 473 bp in chromosome 11p13, using Integrative Genomics Viewer and AnnotSV software. CONCLUSION: WAGR syndrome is a rare contiguous gene deletion syndrome with a greater risk of developing Wilms tumour associated with Peters' anomaly and congenital aniridia. However, co-occurrence of both anomalies was rarely reported in twins, and never in both eyes of monozygotic twins. Here, we report the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins with WAGR syndrome.
Assuntos
Aniridia , Opacidade da Córnea , Gêmeos Monozigóticos , Síndrome WAGR , Tumor de Wilms , Humanos , Feminino , Gêmeos Monozigóticos/genética , Síndrome WAGR/genética , Aniridia/genética , Aniridia/complicações , Tumor de Wilms/genética , Tumor de Wilms/complicações , Lactente , Opacidade da Córnea/genética , Segmento Anterior do Olho/anormalidades , Segmento Anterior do Olho/diagnóstico por imagem , Anormalidades do Olho/genética , Anormalidades do Olho/diagnóstico por imagem , Anormalidades do Olho/complicações , Doenças em Gêmeos/genética , Neoplasias Renais/genética , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/complicaçõesRESUMO
ABSTRACT Aniridia is a congenital eye disorder with a variable degree of hypoplasia or absence of iris tissue. It is caused by loss of function of the PAX6 gene and may be an isolated ocular abnormality or part of a syndrome. WAGRO refers to a rare genetic condition leading to Wilms tumor, aniridia, genitourinary anomalies, mental retardation, and obesity and is caused by a deletion of the short arm of chromosome 11 (11p), where the PAX6 gene is located. Here, we report on an 8-year-old boy with aniridia, polar cataract, and lens subluxation along with neuropsychomotor and speech delays. Karyotype evaluation showed an interstitial deletion including region 11p13-p14, confirming the diagnosis of WAGRO syndrome. In cases of aniridia, a diagnosis of WAGRO syndrome should be considered.
RESUMO A aniridia é uma doença ocular congênita com grau variável de hipoplasia ou ausência do tecido da íris. É causada pela perda de função do gene PAX6 e pode ser uma anormalidade ocular isolada ou parte de uma síndrome. WAGRO refere-se a uma condição genética rara que leva ao tumor de Wilms, aniridia, anomalias geniturinárias, déficit intelectual e obesidade e é causada por uma deleção do braço curto do cromossomo 11 (11p), onde o gene PAX6 está localizado. Aqui, nós relatamos um menino de 8 anos de idade com aniridia, catarata polar e subluxação do cristalino, além de retardo neuropsicomotor e de fala. A avaliação cariotípica revelou uma deleção intersticial envolvendo a região 11p13-p14, confirmando o diagnóstico da síndrome WAGRO. Em casos de aniridia, um diagnóstico de síndrome de WAGRO deve ser considerado.
Assuntos
Humanos , Masculino , Criança , Catarata/diagnóstico , Aniridia/diagnóstico , Subluxação do Cristalino/diagnóstico , Síndrome WAGR/diagnóstico , Obesidade/diagnóstico , Catarata/genética , Cromossomos Humanos Par 11/genética , Aniridia/genética , Subluxação do Cristalino/genética , Deleção Cromossômica , Síndrome WAGR/genética , Cariótipo , Obesidade/genéticaRESUMO
Aniridia is a congenital eye disorder with a variable degree of hypoplasia or absence of iris tissue. It is caused by loss of function of the PAX6 gene and may be an isolated ocular abnormality or part of a syndrome. WAGRO refers to a rare genetic condition leading to Wilms tumor, aniridia, genitourinary anomalies, mental retardation, and obesity and is caused by a deletion of the short arm of chromosome 11 (11p), where the PAX6 gene is located. Here, we report on an 8-year-old boy with aniridia, polar cataract, and lens subluxation along with neuropsychomotor and speech delays. Karyotype evaluation showed an interstitial deletion including region 11p13-p14, confirming the diagnosis of WAGRO syndrome. In cases of aniridia, a diagnosis of WAGRO syndrome should be considered.
Assuntos
Aniridia/diagnóstico , Catarata/diagnóstico , Subluxação do Cristalino/diagnóstico , Obesidade/diagnóstico , Síndrome WAGR/diagnóstico , Aniridia/genética , Catarata/genética , Criança , Deleção Cromossômica , Cromossomos Humanos Par 11/genética , Humanos , Cariótipo , Subluxação do Cristalino/genética , Masculino , Obesidade/genética , Síndrome WAGR/genéticaRESUMO
Gillespie syndrome (GS) [MIM: 206700] is a very rare condition characterized by bilateral iris defect, congenital hypotonia, cerebellar ataxia and intellectual disability. The typical iris anomaly is considered necessary to the diagnosis of GS. Recently, variants in ITPR1 were described causing GS. Non-neurological features were reported in few patients. Here we describe two consanguineous siblings with GS and a novel homozygous ITPR1 pathogenic variant (p.N984fs). They also present a cardiac defect (pulmonary valve stenosis) and one sib had a genitourinary malformation (ureteropelvic junction obstruction). Our report reinforces ITPR1 as the cause of GS and suggests a possible role of ITPR1 in the development of other organs.
Assuntos
Aniridia/genética , Aniridia/patologia , Ataxia Cerebelar/genética , Ataxia Cerebelar/patologia , Homozigoto , Receptores de Inositol 1,4,5-Trifosfato/genética , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Mutação , Brasil , Pré-Escolar , Consanguinidade , Feminino , Humanos , Lactente , Masculino , Linhagem , IrmãosRESUMO
IMPORTANCE: The importance of the study was to describe the clinical characteristics and mutational analysis of Mexican patients with aniridia. BACKGROUND: Aniridia is a panocular hereditary eye disease caused by mutations in the PAX6 transcription factor. Mutation detection rate is highly variable ranging from 30% to 90% in different populations. Very few studies have been published about the PAX6 mutational analysis in aniridia patients from Mexico. In order to establish a more representative PAX6 mutational frequency in the country, a cohort of 22 Mexican unrelated aniridia probands were analysed in this study. DESIGN: Case series. PARTICIPANTS: A total of 22 Mexican probands with bilateral isolated aniridia and their available relatives were included. METHODS: Sanger sequencing was used for the mutational analysis of all coding exons and flanking intronic regions of PAX6. MAIN OUTCOME MEASURES: Clinical characteristics and results of PAX6 mutational analysis in probands with aniridia and available family members. RESULTS: Molecular analysis of PAX6 in 22 index cases with aniridia allowed the identification of a total of 16 different mutations. Seven of these pathogenic variants are novel, including c.183C>G, p.(Y61*); c.718delC, p.(R240Efs*3); c.1149_1152delTCAG, p.(P385Wfs*139); c.257_266delAAATAGCCCA, p.(K86Sfs*35); c.836_843dupGCAACACA p.(P282Afs*86); c.1032+2_1032+3insT; and c.141+2T>A. Inter and intrafamilial phenotypic heterogeneity was found. CONCLUSIONS AND RELEVANCE: The mutational diagnostic rate in this series was 77%, which is comparable with reports from other populations. Importantly, no founder mutations were identified in this case series. Our results add 7 novel PAX6 pathogenic variants to the aniridia-related mutational spectrum and reveal considerable PAX6 allelic heterogeneity in this population.
Assuntos
Aniridia/genética , DNA/genética , Mutação , Fator de Transcrição PAX6/genética , Adolescente , Adulto , Alelos , Aniridia/epidemiologia , Aniridia/metabolismo , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Heterogeneidade Genética , Humanos , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Fator de Transcrição PAX6/metabolismo , Fenótipo , Adulto JovemRESUMO
Aniridia is an autosomal dominant disorder characterized by the complete or partial loss of the iris and is almost associated with mutations in the paired box gene 6 (PAX6). We examined three generations of a Chinese family with congenital aniridia and observed genetic defects. Exons of PAX6 from 12 family members were amplified by polymerase chain reaction, sequenced, and compared with reference sequences in NCBI reference sequence database (http://www.ncbi.nlm.nih.gov/nuccore/NG_008679.1?from=5001&to=38170&report=genbank). A rare mutation c.2T>A (M1K) in exon 4 of PAX6 was identified in all affected family members but not in unaffected family members. Our results suggest that the c.2T>A (M1K) mutation may be responsible for the pathogenesis of congenital aniridia in this family. To our knowledge, this is the first report of the M1K mutation in PAX6 in a Chinese family with this disease and the second report worldwide.
Assuntos
Aniridia/diagnóstico , Aniridia/genética , Proteínas do Olho/genética , Proteínas de Homeodomínio/genética , Mutação , Fatores de Transcrição Box Pareados/genética , Proteínas Repressoras/genética , Adolescente , Adulto , Sequência de Aminoácidos , Povo Asiático/genética , China , Topografia da Córnea , Análise Mutacional de DNA , Éxons , Proteínas do Olho/química , Família , Feminino , Proteínas de Homeodomínio/química , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/química , Linhagem , Proteínas Repressoras/química , Alinhamento de Sequência , Adulto JovemRESUMO
Congenital aniridia is a rare genetic disorder characterized by varying degrees of iris hypoplasia that are associated with additional ocular abnormalities. More than 90% of the causal mutations identified are found in the PAX6 gene, a transcription factor of critical importance in the process of neurogenesis and ocular development. Here, we investigate clinical, molecular, and craniofacial features of a large Brazilian family with congenital aniridia. Among the 56 eyes evaluated, phenotype variation encompassed bilateral total aniridia to mild iris defects with extensive variation between eyes of the same individual. PAX6 molecular screening indicated a heterozygous splice mutation (c.141 + 1G>A). Thus, we hypothesize that this splicing event may cause variation in the expression of the wild-type transcript, which may lead to the observed variation in phenotype. Affected individuals were more brachycephalic, even though their face height and cephalic circumference were not significantly different when compared to those of non-affected relatives. From this, we infer that the head shape of affected subjects may also be a result of the PAX6 splice-site mutation. Our data summarize the clinical variability associated with the ocular phenotype in a large family with aniridia, and help shed light on the role of PAX6 in neurocranial development.
Assuntos
Aniridia/genética , Aniridia/patologia , Anormalidades Craniofaciais/patologia , Anormalidades do Olho/patologia , Proteínas do Olho/genética , Proteínas de Homeodomínio/genética , Fatores de Transcrição Box Pareados/genética , Fenótipo , Proteínas Repressoras/genética , Adolescente , Adulto , Idoso , Análise de Variância , Sequência de Bases , Brasil , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação/genética , Fator de Transcrição PAX6 , Linhagem , Análise de Sequência de DNARESUMO
Genetic variations within the paired box gene 6 (PAX6) gene are associated with congenital aniridia. To detect the genetic defects in a Chinese twin family with congenital aniridia and nystagmus, exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. Six members from the family of three generations were included in the study. The twins' father presented with congenital aniridia, nystagmus and cataract at birth, while the twins presented with congenital aniridia and nystagmus. A novel mutation c.888 insA in exon 10 of PAX6 was identified in all affected individuals. This study suggests that the novel mutation c.888 insA is likely responsible for the pathogenesis of the congenital aniridia and nystagmus in this pedigree. To the best of our knowledge, this is the first report of this mutation in PAX6 gene in pedigree with aniridia. Furthermore, no PAX6 gene defect was reported in twins with congenital aniridia.
Assuntos
Aniridia/genética , Proteínas do Olho/genética , Proteínas de Homeodomínio/genética , Mutação , Nistagmo Congênito/genética , Fatores de Transcrição Box Pareados/genética , Proteínas Repressoras/genética , Adulto , Aniridia/complicações , Aniridia/diagnóstico , Catarata/complicações , Criança , Éxons , Feminino , Humanos , Masculino , Nistagmo Congênito/complicações , Fator de Transcrição PAX6 , Linhagem , GêmeosRESUMO
Mutations in the PAX6 gene that cause aniridia have been identified in various ethnicities but not in the Malaysian population. Therefore, the objective of this study was to investigate the PAX6 mutation in a Malaysian family with congenital aniridia. In this study, a complete ophthalmic examination was performed on a Dusun ethnic family with aniridia. Genomic DNA was extracted from the peripheral blood of the subjects and screened for the PAX6 gene mutation using polymerase chain reaction amplification high-resolution melting curve analysis (PCR-HRM) followed by confirmation via direct DNA sequencing. A heterozygous G deletion (c.857delG) in exon 7 causing a frame shift in PAX6 was identified in all affected family members. Genotype-phenotype correlation analysis revealed congenital cataract and all affected family members showed a similar spectrum of aniridia with no phenotypic variability but with differences in severity that were age-dependent. In summary, by using a PCR-HRM approach, this study is the first to report a PAX6 mutation in a Malaysian family. This mutation is the cause of the aniridia spectra observed in this family and of congenital cataract.
Assuntos
Aniridia/genética , Proteínas do Olho/genética , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Homeodomínio/genética , Fatores de Transcrição Box Pareados/genética , Polimorfismo Conformacional de Fita Simples/genética , Proteínas Repressoras/genética , Aniridia/patologia , Povo Asiático/genética , Feminino , Estudos de Associação Genética , Humanos , Malásia , Masculino , Mutação , Desnaturação de Ácido Nucleico , Fator de Transcrição PAX6 , LinhagemRESUMO
We report on a boy presenting submucous cleft palate, hydronephrosis, ventriculoseptal defect, aniridia, and developmental delay. Additional material on 11p13 was cytogenetically visible and array analyses identified a duplicated segment on 15q25-26 chromosome region; further, array analyses revealed a small deletion (49 kb) at 11p13 region involving the ELP4 gene and a duplication at 8p23.1. Results were confirmed with both molecular and molecular cytogenetics techniques. Possibilities for etiological basis of clinical phenotype are discussed.
Assuntos
Anormalidades Múltiplas/genética , Aniridia/genética , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 15 , Translocação Genética , Trissomia , Anormalidades Múltiplas/diagnóstico , Aniridia/diagnóstico , Pré-Escolar , Cromossomos Humanos Par 8 , Hibridização Genômica Comparativa , Humanos , Hibridização in Situ Fluorescente , Cariótipo , Masculino , FenótipoRESUMO
PURPOSE: Paired box gene 6 (PAX6) heterozygous mutations are well known to cause congenital non-syndromic aniridia. These mutations produce primarily protein truncations and have been identified in approximately 40%-80% of all aniridia cases worldwide. In Mexico, there is only one previous report describing three intragenic deletions in five cases. In this study, we further analyze PAX6 variants in a group of Mexican aniridia patients and describe associated ocular findings. METHODS: We evaluated 30 nonrelated probands from two referral hospitals. Mutations were detected by single-strand conformation polymorphism (SSCP) and direct sequencing, and novel missense mutations and intronic changes were analyzed by in silico analysis. One intronic variation (IVS2+9G>A), which in silico analysis suggested had no pathological effects, was searched in 103 unaffected controls. RESULTS: Almost all cases exhibited phenotypes that were at the severe end of the aniridia spectrum with associated ocular alterations such as nystagmus, macular hypoplasia, and congenital cataracts. The mutation detection rate was 30%. Eight different mutations were identified: four (c.184_188dupGAGAC, c.361T>C, c.879dupC, and c.277G>A) were novel, and four (c.969C>T, IVS6+1G>C, c.853delC, and IVS7-2A>G) have been previously reported. The substitution at position 969 was observed in two patients. None of the intragenic deletions previously reported in Mexican patients were found. Most of the mutations detected predict either truncation of the PAX6 protein or conservative amino acid changes in the paired domain. We also detected two intronic non-pathogenic variations, IVS9-12C>T and IVS2+9G>A, that had been previously reported. Because the latter variation was considered potentially pathogenic, it was analyzed in 103 healthy Mexican newborns where we found an allelic frequency of 0.1116 for the A allele. CONCLUSIONS: This study adds four novel mutations to the worldwide PAX6 mutational spectrum, and reaffirms the finding that c.969C>T is one of the three more frequent causal mutations in aniridia cases. It also provides evidence that IVS2+9G>A is an intronic change without pathogenic effect.
Assuntos
Indígena Americano ou Nativo do Alasca/genética , Aniridia/genética , Proteínas do Olho/genética , Proteínas de Homeodomínio/genética , Mutação/genética , Fatores de Transcrição Box Pareados/genética , Proteínas Repressoras/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , México , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , Fator de Transcrição PAX6 , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Aniridia is a rare condition whose presence should alert clinicians to the possibility of other abnormalities. One of the differential diagnoses that should be considered is Gillespie syndrome, in which aniridia is associated with cerebellar ataxia and mental retardation. There are only 21 reported cases of Gillespie syndrome. The goal of this paper is to describe the clinical manifestations of a girl born to a consanguineous couple who presented with typical findings of the Gillespie syndrome, in addition to previously undescribed alterations of her distal extremities.
Assuntos
Anormalidades Múltiplas , Aniridia/genética , Ataxia Cerebelar/genética , Consanguinidade , Deficiência Intelectual/genética , Criança , Feminino , Falanges dos Dedos da Mão/diagnóstico por imagem , Humanos , Masculino , Radiografia , Síndrome , Falanges dos Dedos do Pé/diagnóstico por imagemRESUMO
A two-year-old boy presenting with bilateral aniridia and psychomotor retardation had a de novo (2;3;11) highly complex rearrangement which was characterized as far as possible by means of G-banding and FISH assays with multiple probes including cosmids for the Wilms, Aniridia, Genital anomalies and Retardation (WAGR) region, alphoid repeats for chromosomes 2, 3 and 11, subtelomere probes for 2p/2q, 3p/3q and 11q and BACs for 2q32 and 3q13. We identified approximately 15 breakpoints with at least three interchromosomal and three intrachromosome anomalies involving chromosome 11. Both parents had normal karyotypes and no cryptic 11p rearrangements revealed by the chromosome 11 cosmid panel. The lack of a deletion of PAX6 pointed to the direct insertion of an approximately 300-kb segment involving the cosmids FO2121 and AO4160, and more specifically the insertion's proximal breakpoint in the approximately 150-kb segment between FO2121 and FAT5 (PAX6), as the responsible factor for the patient's aniridia via a position effect resulting in functional haploinsufficiency of the PAX6 gene. This case illustrates the importance of recognizing that de novo complex chromosomal rearrangements found in patients with diverse clinical features may contribute to the phenotype, but that multiple mechanisms and higher levels of complexity may be unmasked by high resolution molecular cytogenetic studies.
Assuntos
Aniridia/genética , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 2 , Cromossomos Humanos Par 3 , Pré-Escolar , Bandeamento Cromossômico , Mapeamento Cromossômico , Cosmídeos , Elementos de DNA Transponíveis , Lateralidade Funcional , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Fator de Transcrição PAX5/genética , ProibitinasRESUMO
The authors report on a case of isolated aniridia caused by haploinsufficiency of the PAX6 gene, which is located on 11p13, and a balanced translocation t(5;l1)(p15.3;q22) inherited respectively from his father and his mother. Due to the coincidence of two abnormalities in the same chromosome, the segregation of the mutant allele leading to aniridia and of the chromosomes involved in the translocation are not independent events. Considering that both monosomy and trisomy for 11q22-qter are unviable, his offspring may inherit either the PAX6 mutation or the balanced translocation. However, depending on the occurrence of crossing over, there is a possibility for him to have normal offspring; on the other hand, he may also father children with both anomalies. This unusual case, in which the proband has a presumably very low chance of completely normal offspring, turned to be a challenge for genetic counseling.
Assuntos
Aniridia/genética , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 5/genética , Translocação Genética , Adulto , Troca Genética , Proteínas do Olho/genética , Aconselhamento Genético , Proteínas de Homeodomínio/genética , Humanos , Masculino , Meiose/genética , Mutação , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/genética , Proteínas Repressoras/genéticaRESUMO
PURPOSE: To present the results of molecular analysis of the PAX6 gene in a group of patients with congenital aniridia from Mexican mestizo origin, a previously unstudied ethnic group. METHODS: Five unrelated affected probands, four pertaining to familial cases and one sporadic, were studied at the Institute of Ophthalmology "Conde de Valenciana" in Mexico City. All patients underwent full ophthalmologic examination as well as PAX6 analysis in genomic DNA using a combination of exon-by-exon PCR amplification, direct sequencing, and allele-specific cloning/sequencing. Available affected relatives were also investigated. RESULTS: Three novel intragenic deletions were identified: a 15 bp deletion in exon nine that removes the last two codons of the exon and the first nine bases of intron 10, including the conserved GT splicing donor signal; a 14 bp deletion in exon six that introduces a premature stop signal 15 codons downstream and a four bp deletion in exon seven, which introduces a stop signal 22 codons downstream, in three unrelated probands. Although unrelated, these three latter cases came from the same geographical area, strongly suggesting a founder mutation effect as the source of the anomaly. CONCLUSIONS: Our study provides the first molecular analysis of the PAX6 gene in Mexican subjects with congenital aniridia, identifies three novel intragenic PAX6 deletions, and suggests the occurrence of a PAX6 founder mutation effect in this population. Our results also confirm the current notion that PAX6 truncating mutations are overwhelmingly associated with aniridia regardless of their location in the gene.
Assuntos
Aniridia/genética , Proteínas do Olho/genética , Deleção de Genes , Hispânico ou Latino/genética , Proteínas de Homeodomínio/genética , Fatores de Transcrição Box Pareados/genética , Proteínas Repressoras/genética , Adulto , Sequência de Bases , Criança , Códon , Éxons , Feminino , Efeito Fundador , Humanos , Íntrons , Masculino , México , Dados de Sequência Molecular , Fator de Transcrição PAX6RESUMO
O estudo citogenético convencional em uma menina com aniridia esporádica resultou em uma aparente translocaçäo balanceada t(11;13)(p13;q33) de novo. Entretanto, o estudo citogenético pela hibridaçäo in situ fluorescente (FISH) detectou a presença de uma deleçäo críptica 11p13p14, incluindo a regiäo WAGR e envolvendo aproximadamente 7.5 Mb de DNA, deletando os genes PAX6 e WT1. Estes resultados correlacionam-se com o quadro clínico da paciente e a coloca em alto risco de desenvolver tumor de Wilms. A ausência de retardo mental na paciente indica que a posiçäo distal do ponto de quebra poderá refinar o mapeamento do locus retardo mental na síndrome de genes contíguos WAGR (Wilms, aniridia, anomalias genitais e retardo mental).
Assuntos
Humanos , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Aniridia/genética , Hibridização in Situ Fluorescente , Deleção Cromossômica , Síndrome WAGR/genéticaRESUMO
A aniridia é uma síndrome frequentemente associada a defeitos oculares múltiplos que podem acometer íris, córnea, cristalino, câmara anterior, nervo óptico e retina, além de alteraçöes sistêmicas como Tumor de Wilms, retardo mental, anomalias gênito-urinárias em uma mesma família, onde foram acometidos a mäe, duas filhas e um filho. A herança provável foi autossômica dominante e o estudo do cariótipo mostrou-se normal. O tecido iriano hipolásico foi de difícil visualizaçäo, observado apenas à gonioscopia. Apareceram alteraçöes corneanas como cicatrizes centrais e neovasos periféricos, como um "pannus" em toda a circunferência. Observaram-se grande incdência de catarata e coloboma de cristalino. A hipoplasia de papila ocorreu em todos os casos estudados
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Aniridia/patologia , Câmara Anterior/anormalidades , Córnea/anormalidades , Cristalino/anormalidades , Nervo Óptico/anormalidades , Retina/anormalidades , Aniridia/genéticaRESUMO
The PAX6 gene is expressed at high levels in the developing eye and cerebellum and is mutated in patients with autosomal dominant aniridia. We have tested the role of PAX6 mutations in three families with Gillespie syndrome, a rare autosomal recessive condition consisting of partial aniridia, cerebellar ataxia, and mental retardation. Single-strand conformational polymorphism analysis of affected individuals revealed no alteration of PAX6 sequences. In two families, the disease trait segregates independently from chromosome 11p markers flanking PAX6. We conclude that Gillespie syndrome is genetically distinct from autosomal dominant aniridia.