NGS-Based Genetic Analysis in a Cohort of Italian Patients with Suspected Inherited Myopathies and/or HyperCKemia
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients Cohort
2.2. Genetic Studies
3. Results
3.1. Solved Patients
3.2. Patients with Uncertain Diagnosis
3.2.1. The LPIN1 Example: From Uncertain to Solved Case by RNA Analysis
3.2.2. The CPT2 Example: AR or AD?
3.3. Unsolved Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Munsat, T.L.; Baloh, R.; Pearson, C.M.; Fowler, W. Serum enzyme alterations in neuromuscular disorders. JAMA 1973, 226, 1536–1543. [Google Scholar] [CrossRef]
- Prelle, A.; Tancredi, L.; Sciacco, M.; Chiveri, L.; Comi, G.P.; Martinelli-Boneschi, F.M.; Bagnardi, V.; Battistel, A.; Ciscato, P.; Bordoni, A.; et al. Retrospective study of a large population of patients with asymptomatic or minimally symptomatic raised serum creatine kinase levels. J. Neurol. 2002, 249, 305–311. [Google Scholar] [CrossRef] [PubMed]
- Rowland, L.P.; Willner, J.; DiMauro, S.; Miranda, A. Approaches to the membrane theory of Duchenne muscular dystrophy. In Muscular Dystrophy-Advances and New Trends; Angelini, C., Danieli, G.A., Fontanari, D., Eds.; Excerpta Medica: Amsterdam, The Netherlands, 1980; pp. 3–13. [Google Scholar]
- Khan, F.Y. Rhabdomyolysis: A review of the literature. Neth. J. Med. 2009, 67, 272–283. [Google Scholar] [PubMed]
- Scalco, R.S.; Gardiner, A.R.; Pitceathly, R.D.; Zanoteli, E.; Becker, J.; Holton, J.L.; Houlden, H.; Jungbluth, H.; Quinlivan, R. Rhabdomyolysis: A genetic perspective. Orphanet J. Rare Dis. 2015, 10, 51. [Google Scholar] [CrossRef] [Green Version]
- David, W.S. Myoglobinuria. Neurol. Clin. 2000, 18, 215–243. [Google Scholar] [CrossRef] [PubMed]
- Voermans, N.; Snoeck, M.; Jungbluth, H. RYR1-related rhabdomyolysis: A common but probably underdiagnosed manifestation of skeletal muscle ryanodine receptor dysfunction. Rev. Neurol. 2016, 172, 546–558. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barca, E.; Emmanuele, V.; DiMauro, S. Metabolic Myoglobinuria. Curr. Neurol. Neurosci. Rep. 2015, 15, 69. [Google Scholar] [CrossRef]
- Mochel, F.; Knight, M.A.; Tong, W.-H.; Hernandez, D.; Ayyad, K.; Taivassalo, T.; Andersen, P.M.; Singleton, A.; Rouault, T.A.; Fischbeck, K.H.; et al. Splice Mutation in the Iron-Sulfur Cluster Scaffold Protein ISCU Causes Myopathy with Exercise Intolerance. Am. J. Hum. Genet. 2008, 82, 652–660. [Google Scholar] [CrossRef] [Green Version]
- Legati, A.; Reyes, A.; Nasca, A.; Invernizzi, F.; Lamantea, E.; Tiranti, V.; Garavaglia, B.; Lamperti, C.; Ardissone, A.; Moroni, I.; et al. New genes and pathomechanisms in mitochondrial disorders unraveled by NGS technologies. Biochim. Biophys. Acta 2016, 1857, 1326–1335. [Google Scholar] [CrossRef]
- Nykamp, K.; Anderson, M.; Powers, M.; Garcia, J.; Herrera, B.; Ho, Y.-Y.; Kobayashi, Y.; Patil, N.; Thusberg, J.; Westbrook, M.; et al. Sherloc: A comprehensive refinement of the ACMG–AMP variant classification criteria. Genet. Med. 2017, 19, 1105–1117. [Google Scholar] [CrossRef] [Green Version]
- Nilsson, J.; Schoser, B.; Laforet, P.; Kalev, O.; Lindberg, C.; Romero, N.B.; López, M.D.; Akman, H.O.; Wahbi, K.; Iglseder, S.; et al. Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1. Ann. Neurol. 2013, 74, 914–919. [Google Scholar] [CrossRef] [PubMed]
- Bao, Y.; Kishnani, P.; Wu, J.Y.; Chen, Y.T. Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene. J. Clin. Investig. 1996, 97, 941–948. [Google Scholar] [CrossRef] [Green Version]
- Michot, C.; Hubert, L.; Brivet, M.; De Meirleir, L.; Valayannopoulos, V.; Müller-Felber, W.; Venkateswaran, R.; Ogier, H.; Desguerre, I.; Altuzarra, C.; et al. LPIN1 gene mutations: A major cause of severe rhabdomyolysis in early childhood. Hum. Mutat. 2010, 31, E1564–E1573. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ørngreen, M.C.; Dunø, M.; Ejstrup, R.; Christensen, E.; Schwartz, M.; Sacchetti, M.; Vissing, J. Fuel utilization in subjects with carnitine palmitoyltransferase 2 gene mutations. Ann. Neurol. 2005, 57, 60–66. [Google Scholar] [CrossRef]
- Scalco, R.S.; Snoeck, M.; Quinlivan, R.; Treves, S.; Laforét, P.; Jungbluth, H.; Voermans, N.C. Exertional rhabdomyolysis: Physiological response or manifestation of an underlying myopathy? BMJ Open Sport Exerc. Med. 2016, 2, e000151. [Google Scholar] [CrossRef] [Green Version]
- Nance, J.R.; Mammen, A.L. Diagnostic evaluation of rhabdomyolysis. Muscle Nerve 2015, 51, 793–810. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dosi, C.; Rubegni, A.; Baldacci, J.; Galatolo, D.; Doccini, S.; Astrea, G.; Berardinelli, A.; Bruno, C.; Bruno, G.; Comi, G.P.; et al. Using Cluster Analysis to Overcome the Limits of Traditional Phenotype–Genotype Correlations: The Example of RYR1-Related Myopathies. Genes 2023, 14, 298. [Google Scholar] [CrossRef]
- Rubegni, A.; Malandrini, A.; Dosi, C.; Astrea, G.; Baldacci, J.; Battisti, C.; Bertocci, G.; Donati, M.A.; Dotti, M.T.; Federico, A.; et al. Next-generation sequencing approach to hyperCKemia. Neurol. Genet. 2019, 5, e352. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cavalli, M.; Fossati, B.; Vitale, R.; Brigonzi, E.; Ricigliano, V.A.G.; Saraceno, L.; Cardani, R.; Pappone, C.; Meola, G. Flecainide-Induced Brugada Syndrome in a Patient with Skeletal Muscle Sodium Channelopathy: A Case Report with Critical Therapeutical Implications and Review of the Literature. Front. Neurol. 2018, 9, 385. [Google Scholar] [CrossRef] [Green Version]
- Vivante, A.; Ityel, H.; Pode-Shakked, B.; Chen, J.; Shril, S.; van der Ven, A.T.; Mann, N.; Schmidt, J.M.; Segel, R.; Aran, A.; et al. Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases. Pediatr. Nephrol. 2017, 32, 2273–2282. [Google Scholar] [CrossRef]
- Sambuughin, N.; Mungunsukh, O.; Ren, M.; Capacchione, J.F.; Horkayne-Szakaly, I.; Chuang, K.; Muldoon, S.M.; Smith, J.; O’Connor, F.G.; Deuster, P.A. Pathogenic and rare deleterious variants in multiple genes suggest oligogenic inheritance in recurrent exertional rhabdomyolysis. Mol. Genet. Metab. Rep. 2018, 16, 76–81. [Google Scholar] [CrossRef] [PubMed]
- Legati, A.; Zanetti, N.; Nasca, A.; Peron, C.; Lamperti, C.; Lamantea, E.; Ghezzi, D. Current and New Next-Generation Sequencing Approaches to Study Mitochondrial DNA. J. Mol. Diagn. 2021, 23, 732–741. [Google Scholar] [CrossRef] [PubMed]
- Gemelli, C.; Traverso, M.; Trevisan, L.; Fabbri, S.; Scarsi, E.; Carlini, B.; Prada, V.; Mongini, T.; Ruggiero, L.; Patrone, S.; et al. An integrated approach to the evaluation of patients with asymptomatic or minimally symptomatic hyperCKemia. Muscle Nerve 2022, 65, 96–104. [Google Scholar] [CrossRef]
- Kruijt, N.; van den Bersselaar, L.R.; Kamsteeg, E.J.; Verbeeck, W.; Snoeck, M.M.J.; Everaerd, D.S.; Abdo, W.F.; Jansen, D.R.M.; Erasmus, C.E.; Jungbluth, H.; et al. The etiology of rhabdomyolysis: An interaction between genetic susceptibility and external triggers. Eur. J. Neurol. 2021, 28, 647–659. [Google Scholar] [CrossRef] [PubMed]
(A) Disorders of fatty acid oxidation/lipid metabolism | |||
Gene | Protein | Inheritance | Disease |
ACADM | Medium-chain acyl-CoA Dehydrogenase | AR | Deficiency of medium chain acyl-CoA dehydrogenase |
ACADS | Short-chain acyl-CoA Dehydrogenase | AR | Deficiency of short chain acyl-CoA dehydrogenase |
ACADVL | Very-long-chain acyl-CoA dehydrogenase | AR | Deficiency of very-long-chain acyl-CoA dehydrogenase |
CPT2 | Carnitine palmitoyl-transferase II | AR | Deficiency of Carnitine palmitoyl-transferase 2 |
ETFA | Electron transfer flavoprotein-asubunits | AR | Multiple acyl-coenzyme A dehydrogenase deficiency-Glutaric aciduria type IIA |
ETFB | Electron transfer flavoprotein-bsubunits | AR | Multiple acyl-coenzyme A dehydrogenase deficiency-Glutaric aciduria type IIB |
ETFDH | Electron transfer flavoprotein: ubiquinone oxidoreductase | AR | Multiple acyl-coenzyme A dehydrogenase deficiency-Glutaric aciduria IIC |
FLAD1 | Flavin adenine dinucleotide synthetase | AR | Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency |
HADHA | Hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit | AR | Mitochondrial trifunctional protein deficiency |
HADHB | Hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, beta subunit | AR | Mitochondrial trifunctional protein deficiency |
PNPLA2 | Adipose Triglyceride lipase | AR | Neutral lipid storage disease |
SLC22A5 | Organic cation transporter 2 | AR | Carnitine deficiency, systemic primary |
(B) Disorders of glycogen metabolism | |||
Gene | Protein | Inheritance | Disease |
AGL | Amylo-1,6-Glucosidase, 4-Alpha-Glucanotransferase | AR | Glycogen storage disease IIIa/IIIb, glycogen debrancher enzyme |
ALDOA | Fructose-1,6-bisphosphate aldolase | AR | Glycogen storage disease XII |
ENO3 | Enolase b | AR | Glycogen storage disease XIII |
G6PC | Glucose-6-phosphatase (G6Pase) | AR | Glycogen storage disease Ia |
GAA | Acid Alpha-1,4-Glucosidase (Acid maltase) | AR | Glycogen storage disease II |
GBE1 | 1,4-Alpha-Glucan Branching Enzyme Amylo-(1,4 to 1,6) Transglucosidase Amylo-(1,4 to 1,6) Transglycosylase | AR | Glycogen storage disease IV, Polyglucosan body disease (adult form) |
GYG1 | Glycogenin-1 (glycosyltransferase) | AR | Glycogen storage disease XV, Polyglucosan body myopathy 2 |
GYS1 | Glycogen synthase (mucle) | AR | Glycogen storage disease 0 |
GYS2 | Glycogen synthase (liver) | AR | Glycogen storage disease 0 |
LDHA | Lactate dehydrogenase (muscle, A subunit) | AR | Glycogen storage disease XI |
PFKM | Phosphofructokinase (muscle) | AR | Glycogen storage disease VII, Tarui disease |
PYGB | Glycogen phosphorylase (brain) | AR | Glucogen storage disease V |
PYGL | Glycogen phosphorylase (liver) | AR | Glycogen storage disease VI |
PYGM | Glycogen phosphorylase (muscle) | AR | Glycogen storage disease V, McArdle disease |
PGAM2 | Phosphoglycerate mutase-2 (mucle) | AR | Glycogen storage disease X |
PGK1 | Phosphoglycerate kinase-1 | X-linked | Phosphoglycerate kinase 1 deficiency |
PGM1 | Phosphoglucomutase-1 | AR | Congenital disorder of glycosylation, type 1t Glycogen storage disease XIV |
PHKA1 | Phosphorylase kinase-a1 (muscle) | X-linked | Glycogen storage disease IXd |
PHKA2 | Phosphorylase kinase-a2 (liver) | X-linked | Glycogen storage disease IXa2 |
PHKB | Phosphorylase kinase-b | AR | Glycogen storage disease IXb |
PHKG2 | Phosphorylase kinase-g (liver, testis) | AR | Glycogen storage disease IXc |
PRKAG2 | Noncatalytic gamma subunit of AMP-activated protein kinase | AD | Glycogen storage disease of heart, lethal congenital |
SLC2A2 | Glucose transporter-like (GLUT2) | AR | Fanconi-Bickel syndrome - Glycogen storage disease XI |
SLC37A4 | Glucose-6-PhosphateTransporter 1 | AR | Glycogen storage disease Ib-Ic |
(C) Mitochondrial functions | |||
Gene | Protein | Inheritance | Disease |
ATP5D | Mitochondrial ATP synthase F1 complex-delta subunit | AR | Mitochondrial complex V (ATP synthase) deficiency |
DGUOK | Mitochondrial deoxyguanosine kinase | AR | Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) |
FDX1L | Ferredoxin 1-like ptotein | AR | Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy |
ISCU | Iron-sulfur (Fe-S) clusters scaffold protein | AR | Iron-sulphur cluster deficiency myopathy (mitochondrial disorder) |
HSD17B10 | 2-methyl-3-hydroxybutyryl Co-A dehydrogenase | X-linked | Neurodegenerative disorder, chorioathetosis with mental retardation and abnormal behavior |
LPIN1 | Phosphatidic acid phosphohydrolase 1 | AR | Phosphatidic acid phosphatase deficiency |
POLG | Polymerase gamma | AR/AD | Mitochondrial DNA depletion syndrome Progressive external ophthalmoplegia |
(D) Muscular dystrophies/congenital myopathies | |||
Gene | Protein | Inheritance | Disease |
ANO5 | Transmembrane protein 16E Anoctamin 5 | AR | Miyoshi muscular dystrophy 3 Muscular dystrophy, limb-girdle, autosomal recessive 12 |
CACNA1S | Calcium channel | AD | Malignant hyperthermia susceptibility 5 Thyrotoxic periodic paralysis Hypokalemic periodic paralysis, type 1 |
CAV3 | Caveolin-3 | AD | Myopathy, distal, Tateyama type |
CHKB | Choline kinase | AR | Muscular dystrophy, congenital, megaconial type |
DMD | Dystrophin | X-linked | Duchenne muscular dystrophy, Becker muscular dystrophy |
DYSF | Dysferlin | AR | LGMD2B, Miyoshi myopathy |
FKRP | Fukutin-related protein | AR | LGMD2I |
FKTN | Fukutin | AR | Fukuyama congenital muscular dystrophy |
RBCK1 | RANBP-Type and C3HC4-Type Zinc Finger-Containing 1 | AR | Polyglucosan body myopathy 1 with or without immunodeficiency |
SIL1 | Nucleotide Exchange Factor | AR | Marinesco-Sjogren syndrome |
(E) Disorders of intramuscular calcium release and excitation-contraction coupling | |||
Gene | Protein | Inheritance | Disease |
RYR1 | Skeletal muscle ryanodine receptor 1 | AD/AR | Malignant hyperthermia-susceptibility, Exertional rhabdomyolysis, Congenital myopathy |
N°/Child or Adult | Mutated Gene/Inheritance | RefSeq Match | Reference Group Genes * | cDNA | Protein | ACMG/Franklin Classification | Zygosity | Familiarity |
---|---|---|---|---|---|---|---|---|
1/C | ETFDH/AR | NM_004453.4 | A | c.176-2A>T | splice acceptor variant | P | Homozygous | Not investigated |
2/C | HADHB/AR | NM_000183.3 | A | c.1280G>A c.1370C>T | p.Gly427Glu p.Ala457Val | LP VUS | Compound heterozygous | Mother p.Gly427Glu Father p.Ala457Val |
3/C | RYR1/AD-AR | NM_000540.3 | E | c.10010G>A | p.Arg3337Gln | LP | Heterozygous | Father (s) p.Arg3337Gln Mother negative |
4/C | RYR1/AD-AR | NM_000540.3 | E | c.14918C>T | p.Pro4973Leu | P | Heterozygous | Mother (s) p.Pro4973Leu |
5/C | RYR1/AD-AR | NM_000540.3 | E | c.13490C>G c.4759G>C | p.Pro4497Arg p.Ala1587Pro | VUS VUS | Compound heterozygous | Mother p.Pro4497Arg Father p.Ala1587Pro |
6/C | LPIN1/AR | NM_001261428 | C | c.328C>T c.2395-866_2410-30del | p.Arg110 * p.Glu766_Ser838del | P P | Compound heterozygous | Mother p.Arg110 * Father p.Glu766_Ser838del |
7/A | ANO5/AR | NM_213599.3 | D | c.902G>T c.2516T>G | p.Gly301Val 21 p.Met839Arg | LP LP | Possibly compound heterozygous | Not investigated |
8/A | CPT2/AR-AD | NM_000098.3 | A | c.338C>T | p.Ser113Leu | LP | Homozygous | Not investigated |
9/A | CPT2/AR-AD | NM_000098.3 | A | c.338C>T c.887G>T | p.Ser113Leu p.Arg296Leu | LP VUS | Possibly compound heterozygous | Not investigated |
10/A | ETFDH/AR | NM_004453.4 | A | c.1531G>A c.1832G>A | p.Asp511Asn p.Gly611Glu | VUS LP | Possibly compound heterozygous | Not investigated |
11/A | ETFDH/AR | NM_004453.4 | A | c.250G>A | p.Ala84Thr | P | Homozygous | Not investigated |
12/A | ETFDH/AR | NM_004453.4 | A | c.1249C>T c.1531G>A | p.Gln417Ter p.Asp511Asn | P P | Possibly compound heterozygous | Not investigated |
13/A | ETFDH/AR | NM_004453.4 | A | c.74dupA c.256C>T | p.Tyr25 * p.Arg86Cys | LP VUS | Possibly compound heterozygous | Not investigated |
14/A | ETFDH/AR | NM_004453.4 | A | c.250G>A | p.Ala84Thr | LP | Homozygous | Not investigated |
15/A | ETFDH/AR | NM_004453.4 | A | c.1531G>A | p.Asp511Asn | LP | Homozygous | Not investigated |
16/A | PYGM/AR | NM_005609.4 | B | c.1A>G | p.? | P | Homozygous | Not investigated |
17/A | RBCK1/AR | NM_031229.4 | D | c.896_899delAGTG | p.Glu299Valfs * 46 | P | Homozygous | Not investigated |
18/A | RYR1/AD-AR | NM_000540.3 | E | c.14545G>A | p.Val4849Ile | LP | Heterozygous | Father negative Mother (s) p.Val4849Ile |
19/A | RYR1/AD-AR | NM_000540.3 | E | c.11708G>A | p.Arg3903Gln | P | Heterozygous | Not investigated |
20/A | RYR1/AD-AR | NM_000540.3 | E | c.8594T>C c.6226_6228delA AG | p.Val2865Ala p.Lys2076del | VUS LP | Possibly compound heterozygous | Not investigated |
21/A | RYR1/AD-AR | NM_000540.3 | E | c.12700G>A c.4910C>T | p.Val4234Met p.Ala1637Val | LP VUS | Possibly compound heterozygous | Not investigated |
N°/ Child or Adult | Age/Sex | Alive | CK | RM/Myoglobinuria | CNS Involvement | Muscle Findings | Other |
---|---|---|---|---|---|---|---|
1/C | 13y/M | No | Elevated | No/No | No | Lipid accumulation (muscle and heart) | EMG: myopathy |
2/C | 11y/F | Yes | Mild increase | No/No | No | Neurogenic | Previous episodes of weakness after exertion. An episode of severe limb-girdle and axial weakness with onset due to fever |
3/C | 16y/M | Yes | No | Yes/No | No | Not done | Myalgia, cramps |
4/C | 16y/M | Yes | Mild increase | No/No | No | Absence of alterations | Myalgia and cramps after excercise, family history of hyperckemia and myalgias |
5/C | 12y/F | Yes | Elevated | Yes/No | No | Not done | Myopathy |
6/C | 3y/M | No | Elevated | No/Yes | No | Not done | MR: symmetrical muscular inflammation (legs) |
7/A | 28y/M | Yes | Elevated | No/No | No | Not done | Myalgia, cramps. Proximal Hypostenia (No osteotendinous reflexes) |
8/A | 25y/M | Yes | Elevated | Yes/Yes | No | Not done | Myalgia and fatigue |
9/A | 51y/M | Yes | Elevated | Yes/Yes | No | Not done | Myalgia, muscle weakness |
10/A | 21y/F | Yes | Elevated | No/No | No | Vacuolar myopathy, lipid accumulation | Dicarboxylic aciduria, fatigue and myalgia |
11/A | 42y/M | Yes | Elevated | No/No | No | Lipid accumulation, altered mitochondria | EMG: myopathy |
12/A | 29y/F | Yes | Mild increase | No/No | No | Lipid accumulation | EMG: neurogenic signs |
13/A | 77y/M | Yes | Mild increase | No/No | No | Lipid accumulation | EMG: neurogenic signs |
14/A | 22y/M | Yes | No | No/Yes | No | Not done | Hypostenia, hypotonia (increased liver enzymes, steatosis) |
15/A | unreported/M | Yes | Elevated | No/No | No | Not done | Myalgia, cramps |
16/A | 43y/M | Yes | Elevated | No/Yes | No | Inflammatory necrotizing | Fatigue and cramps |
17/A | 27y/F | Yes | Mild increase | No/No | No | PAS+ | Cardiomyopathy and muscle weakness |
18/A | 25y/M | Yes | Elevated | Yes/No | No | Not done | Cramps, muscle weakness |
19/A | 40y/M | Yes | Elevated | Yes/No | No | Not done | Myalgia, muscle weakness |
20/A | 48y/M | Yes | Elevated | Yes/No | No | Not done | EMG: myopathy |
21/A | 24y/M | Yes | Mild increase | No/No | No | Myogenic signs. Normal electron microscopy | Myalgia, dyspnoea, muscle pain. Psychomotor delay |
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Invernizzi, F.; Izzo, R.; Colangelo, I.; Legati, A.; Zanetti, N.; Garavaglia, B.; Lamantea, E.; Peverelli, L.; Ardissone, A.; Moroni, I.; et al. NGS-Based Genetic Analysis in a Cohort of Italian Patients with Suspected Inherited Myopathies and/or HyperCKemia. Genes 2023, 14, 1393. https://doi.org/10.3390/genes14071393
Invernizzi F, Izzo R, Colangelo I, Legati A, Zanetti N, Garavaglia B, Lamantea E, Peverelli L, Ardissone A, Moroni I, et al. NGS-Based Genetic Analysis in a Cohort of Italian Patients with Suspected Inherited Myopathies and/or HyperCKemia. Genes. 2023; 14(7):1393. https://doi.org/10.3390/genes14071393
Chicago/Turabian StyleInvernizzi, Federica, Rossella Izzo, Isabel Colangelo, Andrea Legati, Nadia Zanetti, Barbara Garavaglia, Eleonora Lamantea, Lorenzo Peverelli, Anna Ardissone, Isabella Moroni, and et al. 2023. "NGS-Based Genetic Analysis in a Cohort of Italian Patients with Suspected Inherited Myopathies and/or HyperCKemia" Genes 14, no. 7: 1393. https://doi.org/10.3390/genes14071393