{Reference Type}: Case Reports
{Title}: How a paternal uniparental isodisomy of chromosome 17 leads to autosomal recessive limb-girdle muscular dystrophy R3.
{Author}: Verebi C;Caumes R;Chantot-Bastaraud S;Deburgrave N;Orhant L;Vaucouleur N;Cuisset L;Bienvenu T;Leturcq F;Nectoux J;
{Journal}: Neuromuscul Disord
{Volume}: 33
{Issue}: 5
{Year}: 2023 05
{Factor}: 3.538
{DOI}: 10.1016/j.nmd.2023.03.004
{Abstract}: 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.