Desmin (DES) gene variant of c.1030T>C from Variant Of Unknown Significance (VOUS) to Significance in Limb Girdle Muscular Dystrophy.



Poster Number: T358


Rafael Vaquer Rivera, MD, Neuromuscular Medicine University of Puerto Rico, Jose Carlo, MD, Neuromuscular Medicine University of Puerto Rico, Brenda Deliz, MD, Neuromuscular Medicine University of Puerto Rico, Alexandra Montalvo Acevedo, MD, University of Puerto Rico, Medical Sciences Campus- MDA Care Center

Limb Girdle Muscular Dystrophies (LGMD) are a subset of heterogenous disorders that tend to affect more men than women and are inherited in an Autosomal Dominant (Type 1) and Autosomal Recessive (Type 2) fashion, with spontaneous variations in some cases. Pathogenic variations to the Desmin (DES) gene have been described in medical literature as LGMD 1E.

We report a Puerto Rican family that has been found with an heterozygous variant, NM_001927.3:c.1030T>C (p.S344P) a DES gene variant that is presently classified as a Variant Of Unknown Significance (VOUS) and is not yet recognized as a formal pathogenic variant. This genetic variant was documented within two out of three generations of the family members with the pathogenic phenotype, since the first known affected member had a LGMD diagnosis based on clinical findings and electrodiagnostic study and died due to progression of disease and cardiac complications prior to the availability of accessible genetic testing for which confirmation of this variant could not be done.

In this reported family, findings correlate with a LGMD 1E phenotype of variable severity, presenting in their late 20’s with predominant foot drop and progressing to proximal weakness, having cardiac and respiratory anomalies, and with relatively normal Creatine Kinase (CK) levels. We believe that the c.1030T>C DES variant that is classified as a VOUS, can be in fact, a significant pathological variant as seen with our family from Puerto Rico.