Ataxia-telangiectasia: an important cause of progressive ataxia and primary immunodeficiency in childhood
Ataxia-telangiectasia: uma causa importante de ataxia progressiva e imunodeficiência primária na infância
Gleyson da Cruz Pinto; Mara Morelo Rocha Felix; Suely Rodrigues dos Santos
Abstract
Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder caused by homozygous or compound heterozygous pathogenic variants in the ataxia telangiectasia mutated (ATM) gene, located at the 11q22-23 locus. This gene encodes a serine/ threonine kinase involved in DNA double-strand break repair, genomic stability, cell cycle control, and apoptosis. The clinical manifestations of AT include cerebellar ataxia, oculocutaneous telangiectasia, primary immunodeficiency, and an increased risk of malignancies. The global incidence of AT ranges from 1:40,000 to 1:300,000 live births. In this report, we describe the case of a 6-year-old girl referred to the Medical Genetics Service for investigation of ataxia and primary immunodeficiency. She was the only child of a young, healthy, nonconsanguineous couple, with no family history of similar cases, malformations, or genetic diseases. The proband presented with the typical AT phenotype, including progressive gait ataxia in childhood, oculocutaneous telangiectasia, and primary immunodeficiency. The diagnosis of AT was confirmed through next-generation sequencing of the ATM gene with copy number variation analysis that identified 2 compound heterozygous pathogenic variants.
Keywords
Resumo
A ataxia-telangiectasia (AT) é uma doença rara de herança autossômica recessiva causada pela presença de variantes patogênicas em homozigose ou heterozigose composta no gene ATM. Este gene, localizado na região cromossômica 11q22-23, codifica uma serina/treonina quinase, cujas funções estão relacionadas ao reparo de quebras de fita dupla do DNA, estabilidade genômica, controle do ciclo celular e apoptose. As manifestações clínicas são caracterizadas por ataxia cerebelar, telangiectasia oculocutânea, imunodeficiência primária e risco aumentado de malignidades. A incidência global de AT é de 1:40.000 a 1:300.000 nascimentos. Probanda, do sexo feminino, 6 anos, encaminhada ao serviço de Genética Médica para investigação de ataxia e imunodeficiência primária. Filha única de casal jovem, saudável, não consanguíneo, sem histórico familiar de outros casos semelhantes, malformações ou doenças genéticas. A probanda apresenta o fenótipo típico de AT com ataxia de marcha progressiva de início na infância, telangiectasia oculocutânea e imunodeficiência primária. O diagnóstico de AT foi confirmado através do sequenciamento por NGS (Next-Generation Sequencing) do gene ATM com análise de CNV (Copy Number Variation) que identificou duas variantes patogênicas em heterozigose composta.
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References
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Submitted date:
07/02/2024
Accepted date:
07/22/2024
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