Limb-Girdle Muscular Dystrophies (LGMDs): The Clinical Application of NGS Analysis, a Family Case Report.

摘要: The diagnosis of LGMD2A (calpainopathy) can be challenging due to genetic heterogeneity and high similarity with other LGMDs or neuromuscular disorders. In this setting, NGS panels are highly recommended perform differential diagnosis, identify new causative mutations enable genotype-phenotype correlations. manuscript, the case a patient affected by is reported, for which application defined custom designed panel allowed confirm calpainopathy linked two heterozygous variants in CAPN3, namely c.550delA c.1813G>C. first variant has been extensively described relation calpainopathy. second c.1813G>C, instead, novel predicted probably damaging. addition, analysis on proband revealed (c.550C>T) LMNA gene, associated dilated cardiomyopathy. deleterious subsequent bioinformatic analysis. Successively, segregation was performed family members. Interestingly, none them showed symptoms but mother diagnosed bradycardia syncopal episodes positive history reported that inherited c.1813G>C (CAPN3) from father who healthy carrier. c.550C>T (LMNA), suggesting thereby possible explanation her cardiovascular problems. Segregation analysis, therefore, confirmed inheritance pattern carried highlighted familiarity cardiomyopathy should not neglected. further partner proband, estimate reproductive risk couple. negative screening, low have an child 50% probability inherit variant. This report clinical utility providing accurate identifying complex phenotypes originating multiple genes. However, results always accomplished dedicated counseling, only evaluate recurrence risks also uncover unexpected findings clinically significant.