How a paternal uniparental isodisomy of chromosome 17 leads to autosomal recessive limb-girdle muscular dystrophy R3.

Camille Verebi, Roseline Caumes, Sandra Chantot-Bastaraud, Nathalie Deburgrave, Lucie Orhant, Nicolas Vaucouleur, Laurence Cuisset, Thierry Bienvenu, France Leturcq, Juliette Nectoux

Neuromuscular disorders : NMD 2023 May

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Uniparental isodisomy is a condition where both chromosomes of a pair are inherited from one parental homologue. If a deleterious variant is present on the duplicated chromosome, its homozygosity can reveal an autosomal recessive disorder in the offspring of a heterozygous carrier. Limb-girdle muscular dystrophy (LGMD) R3 is an autosomal recessive inherited disease that is associated with alpha-sarcoglycan gene (SGCA) variants. We report the first published case of LGMDR3 due to a homozygous variant in SGCA unmasked by uniparental isodisomy. The patient is an 8-year-old who experienced delayed motor milestones but normal cognitive development. He presented with muscle pain and elevated plasma creatine kinase. Sequencing of the SGCA gene showed a homozygous pathogenic variant. Parents were not related and only the father was heterozygous for the pathogenic variant. A chromosomal microarray revealed a complete chromosome 17 copy number neutral loss of heterozygosity encompassing SGCA, indicating paternal uniparental isodisomy. Copyright © 2023 Elsevier B.V. All rights reserved.

Citation

Camille Verebi, Roseline Caumes, Sandra Chantot-Bastaraud, Nathalie Deburgrave, Lucie Orhant, Nicolas Vaucouleur, Laurence Cuisset, Thierry Bienvenu, France Leturcq, Juliette Nectoux. How a paternal uniparental isodisomy of chromosome 17 leads to autosomal recessive limb-girdle muscular dystrophy R3. Neuromuscular disorders : NMD. 2023 May;33(5):367-370