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Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants in ACO2 Gene—Long-Term Follow-Up of a Sibling

Infantile cerebellar-retinal degeneration (ICRD) is an extremely rare, infantile-onset neuro-degenerative disease, characterized by autosomal recessive inherited, global developmental delay (GDD), progressive cerebellar and cortical atrophy, and retinal degeneration. In 2012, a biallelic pathogenic...

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Autores principales: Ha, Dong Jun, Park, Jisun, Seo, Go Hun, Lee, Kyoungyeul, Kwon, Young Se, Lee, Ji Eun, Kim, Su Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965713/
https://www.ncbi.nlm.nih.gov/pubmed/35368710
http://dx.doi.org/10.3389/fgene.2022.729980
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author Ha, Dong Jun
Park, Jisun
Seo, Go Hun
Lee, Kyoungyeul
Kwon, Young Se
Lee, Ji Eun
Kim, Su Jin
author_facet Ha, Dong Jun
Park, Jisun
Seo, Go Hun
Lee, Kyoungyeul
Kwon, Young Se
Lee, Ji Eun
Kim, Su Jin
author_sort Ha, Dong Jun
collection PubMed
description Infantile cerebellar-retinal degeneration (ICRD) is an extremely rare, infantile-onset neuro-degenerative disease, characterized by autosomal recessive inherited, global developmental delay (GDD), progressive cerebellar and cortical atrophy, and retinal degeneration. In 2012, a biallelic pathogenic variant in ACO2 gene (NM_001098.3) was found to be causative of this disease. To date, approximately 44 variants displaying various clinical features have been reported. Here, we report a case of two siblings with compound heterozygous variants in the ACO2 gene. Two siblings without perinatal problems were born to healthy non-consanguineous Korean parents. They showed GDD and seizures since infancy. Their first brain magnetic resonance imaging (MRI), electroencephalography, and metabolic workup revealed no abnormal findings. As they grew, they developed symptoms including ataxia, dysmetria, poor sitting balance, and myopia. Follow-up brain MRI findings revealed atrophy of the cerebellum and optic nerve. Through exome sequencing of both siblings and their parents, we identified the following compound heterozygous variants in the ACO2: c.85C > T (p.Arg29Trp) and c.2303C > A (p.Ala768Asp). These two variants were categorized as likely pathogenic based on ACMG/AMP guidelines. In conclusion, this case help to broaden the genetic and clinical spectrum of the ACO2 variants associated with ICRD. We have also documented the long-term clinical course and serial brain MRI findings for two patients with this extremely rare disease.
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spelling pubmed-89657132022-03-31 Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants in ACO2 Gene—Long-Term Follow-Up of a Sibling Ha, Dong Jun Park, Jisun Seo, Go Hun Lee, Kyoungyeul Kwon, Young Se Lee, Ji Eun Kim, Su Jin Front Genet Genetics Infantile cerebellar-retinal degeneration (ICRD) is an extremely rare, infantile-onset neuro-degenerative disease, characterized by autosomal recessive inherited, global developmental delay (GDD), progressive cerebellar and cortical atrophy, and retinal degeneration. In 2012, a biallelic pathogenic variant in ACO2 gene (NM_001098.3) was found to be causative of this disease. To date, approximately 44 variants displaying various clinical features have been reported. Here, we report a case of two siblings with compound heterozygous variants in the ACO2 gene. Two siblings without perinatal problems were born to healthy non-consanguineous Korean parents. They showed GDD and seizures since infancy. Their first brain magnetic resonance imaging (MRI), electroencephalography, and metabolic workup revealed no abnormal findings. As they grew, they developed symptoms including ataxia, dysmetria, poor sitting balance, and myopia. Follow-up brain MRI findings revealed atrophy of the cerebellum and optic nerve. Through exome sequencing of both siblings and their parents, we identified the following compound heterozygous variants in the ACO2: c.85C > T (p.Arg29Trp) and c.2303C > A (p.Ala768Asp). These two variants were categorized as likely pathogenic based on ACMG/AMP guidelines. In conclusion, this case help to broaden the genetic and clinical spectrum of the ACO2 variants associated with ICRD. We have also documented the long-term clinical course and serial brain MRI findings for two patients with this extremely rare disease. Frontiers Media S.A. 2022-03-11 /pmc/articles/PMC8965713/ /pubmed/35368710 http://dx.doi.org/10.3389/fgene.2022.729980 Text en Copyright © 2022 Ha, Park, Seo, Lee, Kwon, Lee and Kim. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Ha, Dong Jun
Park, Jisun
Seo, Go Hun
Lee, Kyoungyeul
Kwon, Young Se
Lee, Ji Eun
Kim, Su Jin
Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants in ACO2 Gene—Long-Term Follow-Up of a Sibling
title Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants in ACO2 Gene—Long-Term Follow-Up of a Sibling
title_full Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants in ACO2 Gene—Long-Term Follow-Up of a Sibling
title_fullStr Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants in ACO2 Gene—Long-Term Follow-Up of a Sibling
title_full_unstemmed Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants in ACO2 Gene—Long-Term Follow-Up of a Sibling
title_short Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants in ACO2 Gene—Long-Term Follow-Up of a Sibling
title_sort case report: infantile cerebellar-retinal degeneration with compound heterozygous variants in aco2 gene—long-term follow-up of a sibling
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965713/
https://www.ncbi.nlm.nih.gov/pubmed/35368710
http://dx.doi.org/10.3389/fgene.2022.729980
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