ID | Sex | Age (years) | Clinical features | Muscle biopsy/IHC finding | Gene | Mode | Mutation | Inheritance | Novel/reported |
---|---|---|---|---|---|---|---|---|---|
Pathogenic variants | |||||||||
Muscular dystrophy | |||||||||
8 | F | 7.5 | Muscle weakness from 1 to 2 years of age. CK=305 | Marked fibre size variation with endomysial fibrosis. SSCD | COL6A1 | AD | c.1003-2A>G | Maternal, symptomatic | Novel |
9 | M | 6.5 | Muscle weakness from 1 to 2 years of age. Wrist contracture. CK=722 | Marked fibre size variation with endomysial fibrosis. SSCD | COL6A1 | AD | c.1056+1delG | Paternal, symptomatic | Leiden muscular dystrophy pages* |
10 | M | 9.1 | Muscle weakness and joint laxity from birth. CK=462 | Endomysial fibrosis. SSCD | COL6A1 | AD | c.850G>A p.Gly284Arg | De novo | rs12191293823 24 |
22 | M | 13.2 | Muscle weakness from 3 to 4 years of age. Elbow and ankle contracture. CK=286 | Mild necrotic and regenerating process with endomysial fibrosis. SSCD | COL6A1 | AD | c.1002+1delG | De novo | Novel |
31 | F | 8.1 | Muscle weakness from 3 years of age. Ankle contracture. CK=489 | Necrotic and regenerating process. SSCD | COL6A1 | AD | c.877G>A p.Gly293Arg | De novo | rs39812364324 |
41 | F | 6.1 | Muscle weakness with joint laxity from infancy. CK=346 | Moderate fibre size variation with endomysial fibrosis. SSCD | COL6A1 | AD | c.868G>A p.Gly290Arg | De novo | rs12191293924 42 |
46 | M | 5.0 | Muscle weakness from 2 years of age. Joint laxity. CK=308 | Mild necrotic and regenerating process with endomysial fibrosis. SSCD | COL6A3 | AD | c.6210+1G>A p.Gly2053_Pro2070del | De novo | 23 43 |
52 | F | 5.4 | Muscle weakness from 3 years of age. CK=377 | Moderate fibre size variation with endomysial fibrosis. SSCD | COL6A3 | AD | c.6282+1G>C | De novo | Novel |
6 | M | 9.3 | Muscle weakness from 1 to 2 years of age. Neck flexor weakness. Ankle contracture. CK=1071 | Necrotic and regenerating process | LMNA | AD | c.1406T>C p.Ile469Thr | De novo | rs5739469244 |
16 | F | 4.5 | Muscle weakness from infancy. Ankle contracture. CK=975 | Necrotic and regenerating process with inflammation | LMNA | AD | c.745C>T p.Arg249Trp | De novo | rs12191249627 |
55 | F | 8.5 | Muscle weakness with ankle contracture from 1 year of age. CK=1081 | Necrotic and regenerating process | LMNA | AD | c.149G>C p.Arg50Pro | De novo | rs6069535245 |
Congenital myopathy | |||||||||
18 | F | 2.3 | Floppy infant. Myopathic face with high arched palate. CK=130 | Nemaline body myopathy | ACTA1 | AD | c.215C>G p.Pro72Arg | De novo | Leiden muscular dystrophy pages* |
21 | F | 18.7 | Muscle weakness from birth. Motor developmental delay. CK = 10 | Nemaline body myopathy | ACTA1 | AD | c.347C>T p.Ala116Val | De novo | Novel |
40 | F | 15.1 | Muscle weakness from 3 to 4 years of age. Myopathic face with respiratory distress | Myofibrillar disorganisation | SEPN1 | AR | c.1574T>G p.Met525Arg Homozygote | Parents heterozygote | Leiden muscular dystrophy pages* |
24 | M | 17.3 | Motor developmental delay from birth. Myopathic face with high arched palate. Funnel chest. CK=99 | Not available | MTM1 | XR | c.1237A>C p.Ser413Arg Hemizygote | Maternal | Novel |
7 | F | 5.9 | Muscle weakness from infancy. Myopathic face with high arched palate. CK=39 | CFTD | RYR1 | AD/ AR | c.14427C>A p.Phe4809Leu c.14798C>A p.Ile4933Thr | Paternal Maternal | Novel Novel |
Congenital myasthenia | |||||||||
5 | F | 9.3 | Respiratory distress at birth. Motor developmental delay. Myopathic face with high arched palate. Scoliosis | Mild necrotic and regenerating process | DOK7 | AR | c.1185C>G p.Tyr395Ter Homozygote | Parents heterozygote | 46 |
30 | M | 3.1 | Floppy infant | Moderate fibre size variation | AGRN | AR | c.5023G>A p.Gly1675Ser Homozygote | Parents heterozygote | Novel |
11 | M | 16.0 | Muscle weakness from 3 to 4 years of age. Scoliosis. CK=376. | Moderate fibre size variation with endomysial fibrosis | GFPT1 | AR | c.128A>T p.Asp43Val c.706A>T p.Lys236Ter | Paternal Maternal | Novel40 |
Motor Neuron or Peripheral Nerve disease | |||||||||
13 | M | 1.6 | Floppy infant. CK=65 | Grouped atrophy | GARS | AD | c.998A>G p.Glu333Gly | De novo | Novel |
28 | M | 1.9 | Floppy infant | Advanced state pathology | DYNC1H1 | AD | c.3179T>C p.Leu1060Ser | De novo | Novel |
Likely pathogenic variants | |||||||||
Congenital myopathy | |||||||||
4 | F | 16.7 | Muscle weakness from 1 to 2 years of age | Prominent internal nuclei | CCDC78 | AD | c.1133+1G>C | Maternal, no symptoms | Novel |
37 | M | 12.2 | Muscle weakness from 2 years of age. Myopathic face with high arched palate. CK=123 | CFTD | RYR1 | AD/AR | c.14762T>C p.Phe4921Ser | Maternal, no symptoms | Reported as dominant33 |
Muscular dystrophy | |||||||||
29 | F | 6.7 | Hyperflexiblity from birth | Fibre size variation, mild. Endomysial fibrosis. SSCD | COL6A1 | AD | c.1461+3G>C | Paternal, no symptoms | Novel |
48 | M | 7.3 | Muscle weakness from infancy. Joint laxity | Mild necrotic and regenerating process. SSCD | COL6A3 | AD | c.9329-4A>T | NA | Novel rs199800564 |
57 | F | 15.1 | Muscle weakness with ankle contracture from infancy. Scoliosis. CK=610 | Necrotic and regenerating process | RYR1 | AD/ AR | c.1654C>T p.Arg552Trp | Maternal | rs11819215647 |
c.2287G>A p.Val763Met | Paternal | Novel | |||||||
Cardiomyopathy | |||||||||
3 | F | 16.3 | Muscle weakness from infancy. Dilated CMP. CK=38 | Not available | MYBPC3 | AD | c.713G>A p.Arg238His | Maternal, no symptoms | 48 |
Metabolic myopathy | |||||||||
34 | M | 2.9 | Floppy infant. Multiple joint contractures from birth. CK=47 | Small scattered atrophic fibre, type 1 predominance | DNA2 | AD | c.1888C>T p.Gln630Ter | NA | Novel |
Variants of uncertain significance | |||||||||
Congenital myopathy | |||||||||
32 | M | 6.0 | Muscle weakness from 2 to 3 years of age. CK=103 | CFTD | RYR1 | AD/AR | c.2287G>A p.Val763Met | NA | Novel |
33 | M | 7.5 | Muscle weakness from 2 years of age. Myopathic face with high arched palate. CK=70 | Non-specific | RYR1 | AD/ AR | c.3523G>A p.Glu1175Lys | NA | Novel |
Motor neuron or peripheral nerve disease | |||||||||
36 | M | 27.5 | Muscle weakness from birth. Myopathic face. CK=414 | Prominent internal nuclei | DCTN1 | AD | c.2054T>G p.Val685Gly | NA | Novel |
Muscular dystrophy | |||||||||
23 | M | 23.7 | Floppy infant. Myopathic face with high arched palate. CK=374 | Not available | COL6A2 | AD | c.1661A>G p.Lys554Arg | NA | VUS for Emory Genetics Laboratory† |
Variants were heterozygote unless otherwise noted.
Accession numbers utilised for variants annotation: CCDC78 Coiled-coil domain-containing protein 78: NM_001031737.2; MYBPC3 Myosin binding protein C, cardiac : NM_000256.3; AGRN Agrin: NM_198576.3; DNA2 DNA replication helicase/nuclease 2: NM_001080449.2; COL6A1 Collagen VI alfa 1: NM_001848.2, COL6A2 Collagen VI alfa 2: NM_001849.3; COL6A3 Collagen VI alfa 3: NM_004369.3, LMNA Lamin A/C: NM_005572.3, ACTA1 Actin α 1: NM_001100.3, MTM1 Myotubularin 1: NM_000252.2, GARS Glycyl-tRNA synthetase: NM_002047.2, DOK7 Docking protein 7: NM_173660.4, GFPT1 Glutamine-fructose-6-phosphate transaminase 1: NM_001244710.1; DYNC1H1 Dynein cytoplasmic 1 heavy chain 1: NM_001376.4; SEPN1 Selenoprotein N 1: NM_020451.2; RYR1 Ryanodine receptor 1: NM_000540.2; DCTN1 Dynactin 1: NM_004082.4.
*Leiden muscular dystrophy pages at: http://www.dmd.nl/.
†Emory database: http://genetics.emory.edu/egl/emvclass/emvclass.php.
AD, autosomal dominant; AR, autosomal recessive; CK, creatine kinase; CFTD, congenital fibre type disproportion; CMP, cardiomyopathy; IHC, immunohistochemistry; SSCD, sarcolemma specific collagen VI α deficiency; VUS, variants of uncertain significance.