An interesting report of POPDC3 limb girdle muscular dystrophy R26 from India.

Abstract

Introduction: Popeye domain containing 3 (POPDC3) gene encodes a protein involved in membrane trafficking and is highly expressed in skeletal muscles. POPDC3 pathogenic variants are associated with LGMDR26. Only a few reports of POPDC3 LGMD exist worldwide and none from India. Herein, we describe the first case of POPDC3 LGMD26.

Methods: This is a case report from a neurology referral center in India. All the clinical, laboratory and electrophysiological data were collected from the medical records.

Results: A 34-year-old man born to non-consanguineous parents presented with progressive proximal weakness of lower limbs from 22 years of age. He developed calf muscle pain and recurrent falls on walking for 7 years. He had atrophy of calves (medial gastrocnemius more than lateral) along with weakness of hip extensor, adductors and knee flexors and normal upper limb power, resembling Miyoshi myopathy. Serum creatine kinase ranged from 3524 to 6531 U/L. Muscle MRI showed selective atrophy of gluteus maximus, quadriceps femoris, semimembranosus and gastrocnemius with sparing of rectus femoris, gracilis and sartorius. Muscle biopsy done elsewhere and reported to show dystrophic features and immunohistochemistry showed positive staining for dystrophins and sarcoglycans. Clinically the possibility of LGMDR2/Dysferlinopathy, was considered and whole exome sequencing was done which revealed a novel homozygous pathogenic nonsense premature termination codon (PTC) variant (NM_022361.5) c.316C > T (NP_079130.2:) p.Arg106Ter) in exon 2 of POPDC3 gene.

Conclusion: This is the first report of POPDC3- LGMDR26 from India detected among a large cohort (461 genetically confirmed cases). POPDC3 gene variations should be considered in distal onset LGMDs with markedly elevated serum creatine kinase levels.