Monica Traverso
SNUPN gene defect causing early onset progressive LGMD with myofibrillar features
Autori
- MONICA TRAVERSO (IRCC Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy – GENETICA MEDICA)
- MICHELE IACOMINO (Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy – GENETICA MEDICA)
- SERENA BARATTO (Centre of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Genoa, Italy – PATOLOGIA E BIOCHIMICA CLINICA)
- ELENA FAEDO (Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI), University of Genoa – NEUROLOGIA)
- ALESSANDRO GEROLDI (Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI), University of Genoa – GENETICA MEDICA)
- PAOLO UVA (Clinical Bioinformatics Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy – GENETICA MEDICA)
- FEDERICO ZARA (Medical Genetics Unit, IRCCS Istituto; 4Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI), University of Genoa Giannina Gaslini, Genoa, Italy, – GENETICA MEDICA)
- PAOLA MANDICH (6IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI), University of Genoa – GENETICA MEDICA)
- MARINA GRANDIS (IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI), University of Genoa – NEUROLOGIA)
- CHIARA FIORILLO (Child Neuropsychiatry Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI), University of Genoa; – NEUROLOGIA)
Presentatore
MONICA TRAVERSO (IRCC PEDIATRIC NEUROLOGY AND MUSCULAR DISEASES UNIT, IRCCS ISTITUTO GIANNINA GASLINI, GENOA, ITALY)
Modalità
Poster Session
Abstract
“Genetic variants are the main cause of muscular dystrophies, mainly affecting proteins essential for several muscular functions. A large number of genes have already been associated with limb-girdle muscular dystrophies (LGMD) but not all cases have been answered.
Recently a novel biallelic variant in SNUPN gene (p.Ile309Ser) has been associated with LGMD phenotype in two unrelated families.
Snurportin-1, the protein encoded by SNUPN, plays an important role in the nuclear transport of small nuclear ribonucleoproteins (snRNPs), essential components of the spliceosome.
We report on a further LGMD patient in which we identified the same p-Ile309Ser homozygous variant. We confirmed the absence of the SNVs or InDels in-house exome database (BioGeAR) containing ~8000 individuals. We filtered all variants with specific criteria, such as MAF<= 0.01 and high impact in the coding regions.
The patient, a now 38 years old man, was followed by the age of 5 years old for a raised CK and tip-toe ambulation. At age 14 an overt proximal muscle weakness was noted for which he performed a muscle biopsy showing nuclear internalization and abnormalities of the myofibrillar network.
Current neurological examination showed proximal weakness at lower and upper limb and several joint retractions, indicating a LGMD.
Our case confirms that SNUPN variants are related to a new type of muscular dystrophy with myofibrillar /centronuclear features at muscle biopsy and variable clinical phenotypes characterized by early onset progressive proximal weakness, contractures and respiratory involvement. These findings have important implication for clinical diagnosis and genetic counseling.”