Table 1

Pathogenic variants, likely pathogenic variants and variants of uncertain significance in 32 patients

IDSexAge (years)Clinical featuresMuscle biopsy/IHC findingGeneModeMutationInheritanceNovel/reported
Pathogenic variants
Muscular dystrophy
 8F7.5Muscle weakness from 1 to 2 years of age. CK=305Marked fibre size variation with endomysial fibrosis.
SSCD
COL6A1ADc.1003-2A>GMaternal, symptomaticNovel
 9M6.5Muscle weakness from 1 to 2 years of age. Wrist contracture. CK=722Marked fibre size variation with endomysial fibrosis.
SSCD
COL6A1ADc.1056+1delGPaternal, symptomaticLeiden muscular dystrophy pages*
 10M9.1Muscle weakness and joint laxity from birth. CK=462Endomysial fibrosis.
SSCD
COL6A1ADc.850G>A
p.Gly284Arg
De novors12191293823 24
 22M13.2Muscle weakness from 3 to 4 years of age. Elbow and ankle contracture. CK=286Mild necrotic and regenerating process with endomysial fibrosis. SSCDCOL6A1ADc.1002+1delGDe novoNovel
 31F8.1Muscle weakness from 3 years of age. Ankle contracture. CK=489Necrotic and regenerating process.
SSCD
COL6A1ADc.877G>A
p.Gly293Arg
De novors39812364324
 41F6.1Muscle weakness with joint laxity from infancy. CK=346Moderate fibre size variation with endomysial fibrosis.
SSCD
COL6A1ADc.868G>A
p.Gly290Arg
De novors12191293924 42
 46M5.0Muscle weakness from 2 years of age. Joint laxity. CK=308Mild necrotic and regenerating process with endomysial fibrosis. SSCDCOL6A3ADc.6210+1G>A
p.Gly2053_Pro2070del
De novo23 43
 52F5.4Muscle weakness from 3 years of age. CK=377Moderate fibre size variation with endomysial fibrosis.
SSCD
COL6A3ADc.6282+1G>CDe novoNovel
 6M9.3Muscle weakness from 1 to 2 years of age. Neck flexor weakness. Ankle contracture. CK=1071Necrotic and regenerating processLMNAADc.1406T>C
p.Ile469Thr
De novors5739469244
 16F4.5Muscle weakness from infancy. Ankle contracture. CK=975Necrotic and regenerating process with inflammationLMNAADc.745C>T
p.Arg249Trp
De novors12191249627
 55F8.5Muscle weakness with ankle contracture from 1 year of age.
CK=1081
Necrotic and regenerating processLMNAADc.149G>C
p.Arg50Pro
De novors6069535245
Congenital myopathy
 18F2.3Floppy infant. Myopathic face with high arched palate.
CK=130
Nemaline body myopathyACTA1ADc.215C>G
p.Pro72Arg
De novoLeiden muscular dystrophy pages*
 21F18.7Muscle weakness from birth. Motor developmental delay.
CK = 10
Nemaline body myopathyACTA1ADc.347C>T
p.Ala116Val
De novoNovel
 40F15.1Muscle weakness from 3 to 4 years of age. Myopathic face with respiratory distressMyofibrillar disorganisationSEPN1ARc.1574T>G
p.Met525Arg Homozygote
Parents heterozygoteLeiden muscular dystrophy pages*
 24M17.3Motor developmental delay from birth. Myopathic face with high arched palate. Funnel chest. CK=99Not availableMTM1XRc.1237A>C
p.Ser413Arg
Hemizygote
MaternalNovel
 7F5.9Muscle weakness from infancy. Myopathic face with high arched palate. CK=39CFTDRYR1AD/ ARc.14427C>A p.Phe4809Leu
c.14798C>A
p.Ile4933Thr
Paternal
Maternal
Novel
Novel
Congenital myasthenia
 5F9.3Respiratory distress at birth.
Motor developmental delay. Myopathic face with high arched palate. Scoliosis
Mild necrotic and regenerating processDOK7ARc.1185C>G
p.Tyr395Ter
Homozygote
Parents heterozygote46
 30M3.1Floppy infantModerate fibre size variationAGRNARc.5023G>A
p.Gly1675Ser
Homozygote
Parents
heterozygote
Novel
 11M16.0Muscle weakness from 3 to 4 years of age. Scoliosis. CK=376.Moderate fibre size variation with endomysial fibrosisGFPT1ARc.128A>T
p.Asp43Val
c.706A>T
p.Lys236Ter
Paternal
Maternal
Novel40
Motor Neuron or Peripheral Nerve disease
 13M1.6Floppy infant. CK=65Grouped atrophyGARSADc.998A>G
p.Glu333Gly
De novoNovel
 28M1.9Floppy infantAdvanced state pathologyDYNC1H1ADc.3179T>C
p.Leu1060Ser
De novoNovel
Likely pathogenic variants
 Congenital myopathy
 4F16.7Muscle weakness from 1 to 2 years of ageProminent internal nucleiCCDC78ADc.1133+1G>CMaternal, no symptomsNovel
 37M12.2Muscle weakness from 2 years of age. Myopathic face with high arched palate. CK=123CFTDRYR1AD/ARc.14762T>C
p.Phe4921Ser
Maternal, no symptomsReported as dominant33
Muscular dystrophy
 29F6.7Hyperflexiblity from birthFibre size variation, mild. Endomysial fibrosis. SSCDCOL6A1ADc.1461+3G>CPaternal, no symptomsNovel
 48M7.3Muscle weakness from infancy. Joint laxityMild necrotic and regenerating process. SSCDCOL6A3ADc.9329-4A>TNANovel
rs199800564 
 57F15.1Muscle weakness with ankle contracture from infancy. Scoliosis. CK=610Necrotic and regenerating processRYR1AD/ ARc.1654C>T
p.Arg552Trp
Maternalrs11819215647
c.2287G>A
p.Val763Met
PaternalNovel
Cardiomyopathy
 3F16.3Muscle weakness from infancy. Dilated CMP.
CK=38
Not availableMYBPC3ADc.713G>A
p.Arg238His
Maternal, no symptoms48
Metabolic myopathy
 34M2.9Floppy infant. Multiple joint contractures from birth.
CK=47
Small scattered atrophic fibre, type 1 predominanceDNA2ADc.1888C>T
p.Gln630Ter
NANovel
Variants of uncertain significance
Congenital myopathy
 32M6.0Muscle weakness from 2 to 3 years of age. CK=103CFTDRYR1AD/ARc.2287G>A
p.Val763Met
NANovel
 33M7.5Muscle weakness from 2 years of age. Myopathic face with high arched palate. CK=70Non-specificRYR1AD/ ARc.3523G>A
p.Glu1175Lys
NANovel
Motor neuron or peripheral nerve disease
 36M27.5Muscle weakness from birth. Myopathic face. CK=414Prominent internal nucleiDCTN1ADc.2054T>G
p.Val685Gly
NANovel
Muscular dystrophy
 23M23.7Floppy infant. Myopathic face with high arched palate.
CK=374
Not availableCOL6A2ADc.1661A>G
p.Lys554Arg
NAVUS 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.