Table 1 Summary of clinical and molecular data of CMS patients with large deletions in COLQ gene reported in literature in addition to our result
Reference | Ohno et al.,1998 [9] | Wang et al.,2016 [10] | Laforgia et al.,2020 [11] | Luo et al.,2021 [29] | Our study | |
|---|---|---|---|---|---|---|
Sex | M | F | M | M | F | |
Consanguinity | No | No | Yes | No | Yes | |
Age of onset | Birth | 6 years | 55 days | 18 months | 2 months | |
Muscle weakness | Severe | Progressive | Severe | Mild | Mild | |
Ocular abnormality | N/A | No ptosis or double vision | Palpebral ptosis | Ptosis | Ptosis and unilateral partial visual field deficiency | |
Respiratory failure | N/A | N/A | Apnea, respiratory crisis, and cyanosis | - | - | |
Neuromuscular features | Severe myasthenic symptoms | Weakness of neck muscle, proximal upper and lower limbs | Hypotonia, dystonia, electroclinic fits (chaotic movements, hyperextension of arms and legs) | Incapacity to walk steadily and tended to fall | Facial weakness, axial hypotonia, head drop forward, and weakness of neck muscle | |
Deep tendon reflexes | N/A | N | N/A | N/A | - | |
CK level | N/A | N | N/A | N | N | |
(anti-AChR)/ (anti-MuSK) antibodies | (-)/(N/A) | (-)/(-) | (N/A) | (-)/(-) | (-)/(-) | |
ENMG | Decremental response to RNS | Decremental Response to RNS (stimulation at 2 Hz) | Decremental response to RNS (stimulation at 3 Hz) and decrease in the amplitude of MUP | CMAP amplitude increases at low frequency & almost stable at high frequency | Decremental response to RNS (stimulation at 3 Hz) | |
Mutation | c.[(106+1_107-1)_(321+1_322-1)del]; [640G>T] | c.[(954+1_955-1)_(1195+1_1196-1)del]; [1298+3A>G] | arr [GrCh37]3p25.1(15491478x1,15492150_15511615x0,15511740x1) | c.(954+1_955-1)_(1195+1_1196-1)del | c.(814+1_815-1)_(954+1_955-1)del | |
Genotype | Compound heterozygous | Compound heterozygous | Homozygous | Homozygous | Homozygous | |
Paternal allele | Variation | c.640G>T p.(Glu214*) | c.1298+3A>G p.(?) | arr [GrCh37]3p25.1(15491478x1,15492150_15511615x0,15511740x1) p.(?) | c.(954+1_955-1)_(1195+1_1196-1) del p.(Ile319Alafs*27) | c.(814+1_815-1)_(954+1_955-1) del p.(Gly272Aspfs*11) |
Domain | Distal third of collagen-like domain | C-terminal region | Distal third of collagen-like domain and the entire C-terminal region | Distal third of collagen-like domain and proximal C-terminal region | Distal third of collagen-like domain | |
Maternal allele | Variation | c.(106+1_107-1)_(321+1_322-1) del p.(Ala36Glyfs*26) | c.(954+1_955-1)_(1195+1_1196-1) del p.(Ile319Alafs*27) | arr [GrCh37]3p25.1(15491478x1,15492150_15511615x0,15511740x1) p.(?) | c.(954+1_955-1)_(1195+1_1196-1) del p.(Ile319Alafs*27) | c.(814+1_815-1)_(954+1_955-1) del p.(Gly272Aspfs*11) |
Domain | N-terminal region (PRAD domain) | Distal third of collagen-like domain and proximal C-terminal region | Distal third of collagen-like domain and the entire C- terminal region | Distal third of collagen-like domain and proximal C-terminal region | Distal third of collagen-like domain | |
Treatment | Response unfavorably to anticholinesterase medications | N/A | Response favorably to 3–4 diaminopyridine and salbutamol | Response favorably to salbutamol | Response favorably to salbutamol | |
Evolution | N/A | Waddling gait, walk until 600 feet at 16 years | Walk with support. NIV during sleep at 20 months | Walk longer at 12 years | Walk without support at 28 months | |