Beyond the exome: a very complex diagnosis of myofibrillar myopathy solved by genomic long read sequencing

Elenco Abstract

Annalaura Torella

Beyond the exome: a very complex diagnosis of myofibrillar myopathy solved by genomic long read sequencing

Autori

ANNALAURA TORELLA (DEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGI VANVITELLI”, NAPLES, ITALY – GENETICA MEDICA)
GIULIO PILUSO (DEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGI VANVITELLI”, NAPLES, ITALY – )
MARIA ELENA ONORE (DEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGI VANVITELLI”, NAPLES, ITALY – )
PASQUALE PRIMO (DEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGI VANVITELLI”, NAPLES, ITALY – )
PASQUALE DI LETTO (DEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGI VANVITELLI”, NAPLES, ITALY – )
MARIATERESA ZANOBIO (DEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGIDEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGI VANVITELLI”, NAPLES, ITALY VANVITELLI”, NAPLES, ITALY – )
CARMINE SPAMPANATO (DEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGI VANVITELLI”, NAPLES, ITALY – )
GERMAN DEMIDOV (INSTITUTE OF MEDICAL GENETICS AND APPLIED GENOMICS, UNIVERSITY OF TÜBINGEN, TÜBINGEN, GERMANY – )
VIVIANA CETRANGOLO (DEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGIDEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGI VANVITELLI”, NAPLES, ITALY VANVITELLI”, NAPLES, ITALY – )
SARAH IFFAT RAHMAN (DEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGIDEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGI VANVITELLI”, NAPLES, ITALY VANVITELLI”, NAPLES, ITALY – )
FRANCESCA TORRI (DEPARTMENT OF CLINICAL AND EXPERIMENTAL MEDICINE, UNIVERSITY OF PISA, PISA, ITALY – )
GIULIA RICCI (DEPARTMENT OF CLINICAL AND EXPERIMENTAL MEDICINE, UNIVERSITY OF PISA, PISA, ITALY – )
GABRIELE SICILIANO (DEPARTMENT OF CLINICAL AND EXPERIMENTAL MEDICINE, UNIVERSITY OF PISA, PISA, ITALY – )
VINCENZO NIGRO (DEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGIDEPARTMENT OF PRECISION MEDICINE, UNIVERSITY OF CAMPANIA “LUIGI VANVITELLI”, NAPLES, ITALY VANVITELLI”, NAPLES, ITALY – )

Presentatore

ANNALAURA TORELLA

Modalità

Oral Communication

Abstract

“We report a family in whom several years ago clinical suspicion of distal myopathy was proposed. The proband was affected by an early-onset distal myopathy with abnormalities compatible with myofibrillar myopathy at the muscle biopsy and dilatative cardiomyopathy treated with heart transplant at 18 years of age and her mother showed progressive limb-girdle weakness and hyperCKemia from the age of 45.
Trio whole exome sequencing (WES) did not identify any causative variants associated with autosomal dominant myofibrillar myopathy. WES data from our neuromuscular cohort were submitted to Solve-RD and re-analysed.
Data reanalysis was able to identify a structural variation not coincident between mother and child. A 3.4 kb deletion was detected in the affected mother and a 2.9 kb deletion in her affected son. Both alterations include part of DES gene, respectively from promoter to exon 4 and from exon 4 to exon 6, confirmed by in house custom CGH-array, ACACIA. However, by Sanger Sequencing in the mother were identified the breakpoints of both alterations. To unravel the non-coincident result long read sequencing by Oxford Nanopore were performed. In the mother blood cells the 2.9 kb deletion is seen in a very low percentage of long reads obtained (2.5%), highlighting the presence of a mosaicism.
Our results confirm the suspected diagnosis and show the first reported case of familiar distal myopathy caused by a complex chromosomal alteration and it highlights how genomic long read sequencing-based approach can increase the diagnostic rate in rare diseases.”