Pseudodominance in Friedreich Ataxia-Impact of High Prevalence of Carriers and Intrafamilial Clinical Variation.

Autor: Malaquias MJ; Neurology Department Centro Hospitalar Universitário do Porto Porto Portugal., Oliveira J; Unidade de Investigação Genética e Epidemiológica em Doenças Neurológicas (UnIGENe), Institute for Molecular and Cell Biology (IBMC), Instituto de Investigação e Inovação em Saúde (i3S) Universidade do Porto Porto Portugal.; Centre for Predictive and Preventive Genetics (CGPP), Institute for Molecular and Cell Biology (IBMC), Instituto de Investigação e Inovação em Saúde (i3S) Universidade do Porto Porto Portugal., Santos M; Paediatric Neurology Unit, Centro Materno-Infantil do Norte Centro Hospitalar Universitário do Porto Porto Portugal., Brandão AF; Unidade de Investigação Genética e Epidemiológica em Doenças Neurológicas (UnIGENe), Institute for Molecular and Cell Biology (IBMC), Instituto de Investigação e Inovação em Saúde (i3S) Universidade do Porto Porto Portugal., Sardoeira A; Neurology Department Centro Hospitalar Universitário do Porto Porto Portugal., Sequeiros J; Unidade de Investigação Genética e Epidemiológica em Doenças Neurológicas (UnIGENe), Institute for Molecular and Cell Biology (IBMC), Instituto de Investigação e Inovação em Saúde (i3S) Universidade do Porto Porto Portugal.; Centre for Predictive and Preventive Genetics (CGPP), Institute for Molecular and Cell Biology (IBMC), Instituto de Investigação e Inovação em Saúde (i3S) Universidade do Porto Porto Portugal.; ICBAS School of Medicine and Biomedical Sciences Porto Portugal., Barros J; Neurology Department Centro Hospitalar Universitário do Porto Porto Portugal.; ICBAS School of Medicine and Biomedical Sciences Porto Portugal., Damásio J; Neurology Department Centro Hospitalar Universitário do Porto Porto Portugal.; Unidade de Investigação Genética e Epidemiológica em Doenças Neurológicas (UnIGENe), Institute for Molecular and Cell Biology (IBMC), Instituto de Investigação e Inovação em Saúde (i3S) Universidade do Porto Porto Portugal.; Centre for Predictive and Preventive Genetics (CGPP), Institute for Molecular and Cell Biology (IBMC), Instituto de Investigação e Inovação em Saúde (i3S) Universidade do Porto Porto Portugal.
Jazyk: angličtina
Zdroj: Movement disorders clinical practice [Mov Disord Clin Pract] 2023 Feb 25; Vol. 10 (4), pp. 670-676. Date of Electronic Publication: 2023 Feb 25 (Print Publication: 2023).
DOI: 10.1002/mdc3.13694
Abstrakt: Background: Friedreich ataxia (FA) is the most common form of autosomal recessive (AR) ataxia. It is a rare disease, but carriers are frequent (1/100). Pseudodominance in FA has seldomly been reported; it may pose additional challenges for diagnosis.
Cases: A family with two consecutive generations affected by FA is described. The proband and two younger siblings had typical FA, characterized by infantile-onset ataxia, hyporeflexia, Babinski sign, cardiomyopathy, and loss of ambulation in the second decade of life. Another female sibling had delayed-onset (>25 years old), with mild cerebellar and sensitive ataxia since her mid-30s. Their father presented very late-onset FA (>40 years old), with sensitive axonal neuropathy. All five patients had biallelic (GAA) n expansion in FXN . The first three had larger expansions (>800 repeats), while the latter two had one shorter expanded allele (~90 repeats).
Literature Review: Pseudodominant inheritance has been described in 13 neurological disorders. Seven are movement disorders, of which three were associated with high frequency of carriers (FA, Wilson's disease and PRKN -related parkinsonism).
Conclusions: Clinicians should be aware of the possibility of pseudodominance when facing an apparent autosomal dominant pedigree, particularly in disorders with high frequency of carriers and variable expression. Otherwise, genetic diagnoses may be delayed.
(© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
Databáze: MEDLINE
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