Table 1.
Clinical and genetic findings of the ANO5 patients
| Patients | Onset | CK (U/L) | Pattern of muscle involvement | Mutations | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| # | Age/sex | Age at onset | Initial symptoms | Atrophy | Physical examination summary | Functional status | Phenotype | Other features | Allele 1 | Allele 2 | |
| 1.1 | 18/M | 12 | Myalgia, exercise intolerance | 5665 | None | Normal | Ambulant | Pseudometabolic | c.191dupA, p.Asn64Lys | c.191dupA, p.Asn64Lys | |
| 1.2 | 18/F | 18 | Asymptomatic hyperCKemia | 4008 | None | Normal | Ambulant | HyperCKemia | Calf hypertrophy | c.191dupA, p.Asn64Lys | c.191dupA, p.Asn64Lys |
| 2 | 43/M | 37 | Mild lower limbs weakness | 4512 | None | Proximal and distal weakness (MRC 4) | Ambulant | LGMD | Dysphagia, calf hypertrophy | c.692G > T, p.Gly231Val | c.1359C > G, p.(Tyr453*) |
| 3 | 48/M | 42 | Mild lower limbs weakness | 3897 | None | Proximal lower limb weakness (MRC 4) | Ambulant | LGMD | Dysphagia | c.191dupA, p.Asn64Lys | c.191dupA, p.Asn64Lys |
| 4 | 12/M | 11 | Asymptomatic hyperCKemia | 8928 | None | Normal | Ambulant | HyperCKemia | c.172C > T, p.Arg58Trp | c.172C > T, p.Arg58Trp | |
| 5 | 62/M | 54 | Mild lower limbs weakness | 7533 | Biceps and quadriceps (moderate) | Proximal and distal weakness (MRC 4) | Ambulant | LGMD | Asymmetry | c.692G > T, p.Gly231Val | c.1359C > G, p.(Tyr453*) |
| 6 | 40/M | 20 | Lower limbs weakness with myalgia | 5450 | Deltoids, biceps and quadriceps (moderate) | Neck (MRC 4), proximal (MRC 3) and distal (MRC 4) weakness | Assisted walking | LGMD | Asymmetry | c.692G > T, p.Gly231Val | c.692G > T, p.Gly231Val |
| 7 | 55/M | 35 | Exercise intolerance | 4806 | Biceps, triceps and quadriceps (severe) | Proximal and distal weakness (MRC 4) | Ambulant | LGMD | Asymmetry | c.1898 + 1G>A, p.(?) | c.2012A > G, p.Tyr671Cys |
| 8 | 48/M | 34 | Exercise intolerance | 4467 | Pectoralis (mild) | Proximal lower limb weakness (MRC 4) | Ambulant | LGMD | Dysphagia, calf hypertrophy | c.172C > T, p.Arg58Trp | c.172C > T, p.Arg58Trp |
| 9 | 68/F | 58 | Myalgia, exercise intolerance | 2051 | Gastrocnemius (mild) | Trunk (MRC 3) weakness | Ambulant | Pseudometabolic | Restrictive respiratory involvement (FVC 75%) | c.692G > T, p.Gly231Val | c.692G > T, p.Gly231Val |
| 10 | 66/M | 56 | Mild lower limb weakness | 882 | Quadriceps (severe) | Proximal lower limb weakness (MRC 4) | Ambulant | LGMD | c.368C > T, p.Ser123Leu | c.368C > T, p.Ser123Leu | |
| 11 | 66/M | 58 | Lower limb weakness with myalgia | 1802 | Biceps, triceps (moderate), quadriceps and gastrocnemius (severe) | Neck (MRC4) and proximal (MRC 3) weakness | Wheelchair bounded | LGMD | c.191dupA, p.Asn64Lys | c.191dupA, p.Asn64Lys | |
| 12.1 | 52/M | 40 | Mild lower limb weakness | 10679 | None | Biceps and quadriceps weakness (MRC 4) | Ambulant | LGMD | Calf hypertrophy | c.191dupA, p.Asn64Lys | c.2012A > G, p.Tyr671Cys |
| 12.2 | 50/F | 44 | Myalgia, exercise intolerance | 1138 | None | Normal | Ambulant | Pseudometabolic | Calf hypertrophy | c.191dupA, p.Asn64Lys | c.2012A > G, p.Tyr671Cys |
| 13 | 66/F | 52 | Lower limb weakness with myalgia | 2179 | Quadriceps (severe) | Neck and proximal weakness (MRC 4) | Ambulant | LGMD | Asymmetry, calf hypertrophy | c.1359C > G, p.(Tyr453*) | c.689A > G, p.Asp230Gly |
| 14 | 63/M | 40 | Myalgia | 913 | None | Normal | Ambulant | Pseudometabolic | c.692G > T, p.Gly231Val | c.692G > T, p.Gly231Val | |
| 15 | 37/M | 28 | Progressive lower limbs weakness | 12640 | Quadriceps (mild) and gastrocnemius (severe) | Proximal (MRC 4) and distal weakness (MRC 3) | Ambulant | LGMD | Asymmetry, mild restrictive respiratory involvement (FVC 74%) | c.1210 C > T, p.(Arg404*) | c.1210 C > T, p.(Arg404*) |
| 16 | 53/F | 48 | Myalgia, exercise intolerance | 1850 | Gastrocnemius (severe) | Neck (MRC 3) and lower limb weakness (MRC 4) | Assisted walking | LGMD | Severe restrictive respiratory involvement (FVC 27%) with dyspnoea | c.1210 C > T, p.(Arg404*) | c.1210 C > T, p.(Arg404*) |
| 17 | 61/F | 49 | Myalgia, exercise intolerance | 7500 | Deltoids, biceps, gastrocnemius (moderate), quadriceps (severe) | Trunk and proximal weakness (MRC 4) | Ambulant | LGMD | Asymmetry | c.191dupA, p.Asn64Lys | c.191dupA, p.Asn64Lys |
| 18 | 19/M | 14 | Lower limb weakness with myalgia | 2800 | Glutei (mild) | Proximal weakness (MRC 4) | Ambulant | LGMD | Calf hypertrophy | c.191dupA, p.Asn64Lys | c.1295C > G, p.Ala432Gly |
| 19 | 45/M | 38 | Progressive lower limbs weakness | 8550 | Biceps and quadriceps (mild) | proximal weakness (MRC 4) | Ambulant | LGMD | c.191dupA, p.Asn64Lys | c.692G > T, p.Gly231Val | |
| 20 | 72/M | 67 | Progressive lower limbs weakness | 20000 | Deltoids, biceps, gastrocnemius and quadriceps (moderate) | Trunk (MRC 3), proximal and distal (MRC 4) weakness | Assisted walking | LGMD | Asymmetry, hypertrophic cardiomyopathy | c.191dupA, p.Asn64Lys | c.2498T > A, p.Met833Lys |
| 21 | 44/M | 37 | Lower limb weakness with myalgia | 1198 | Quadriceps and gastrocnemius (severe) | Trunk and proximal (MRC 4) weakness | Ambulant | LGMD | c.692G > T, p.Gly231Val | c.2498T > A, p.Met833Lys | |
| 22 | 54/F | 42 | Progressive proximal weakness | 505 | Biceps (mild) and quadriceps (moderate) | Proximal and distal weakness (MRC 4) | Ambulant | LGMD | Calf hypertrophy | c.191dupA, p.Asn64Lys | c.2272C > T, p.Arg758Cys |
| 23 | 25/M | 25 | Rhabdomyolysis | 47562 | None | Normal | Ambulant | Pseudometabolic | Calf hypertrophy | c.191dupA, p.Asn64Lys | c.2272C > T, p.Arg758Cys |
| 24 | 40/M | 32 | Asymptomatic hyperCKemia | 12000 | None | Normal | Ambulant | HyperCKemia | c.191dupA, p.Asn64Lys | c.692G > T, p.Gly231Val | |
| 25 | 36/M | 28 | Lower limb weakness with myalgia | 950 | Deltoids, biceps, glutei and quadriceps (moderate) | Proximal weakness (MRC 4) | Ambulant | LGMD | Calf hypertrophy | 191dupA, p.Asn64Lys | c.2311_2312delCA, p.Gln771Alafs |
| 26 | 53/M | 50 | Rapid onset proximal weakness | 32105 | Deltoids, biceps, gastrocnemius (moderate), quadriceps (severe) | Trunk (MRC 3) and proximal (MRC 4) weakness | Assisted walking | LGMD | Asymmetry | 191dupA, p.Asn64Lys | c.2498T > A, p.Met833Lys |
| 27 | 27/F | 22 | Exercise intolerance | 2223 | Deltoids, biceps, quadriceps and gastrocnemius (mild) | Proximal weakness (MRC 4) | Assisted walking | LGMD | c.2272C > T, p.Arg758Cys | c.1295C > G, p.Ala432Gly | |
| 28 | 42/M | 40 | Lower limb weakness with myalgia | 3600 | Quadriceps and gastrocnemius (moderate) | Proximal and distal weakness (MRC 4) | Ambulant | LGMD | Asymmetry | 191dupA, p.Asn64Lys | c.2272C > T, p.Arg758Cys |
| 29.1 | 46/M | 39 | Lower limb weakness with myalgia | 20540 | Quadriceps (moderate) | Proximal lower limb weakness (MRC 4) | Ambulant | LGMD | Asymmetry | 191dupA, p.Asn64Lys | c.2498T > A, p.Met833Lys |
| 29.2 | 49/M | 30 | Myalgia and hyperCKemia | 3789 | Gastrocnemius (mild) | Normal | Ambulant | Pseudometabolic | 191dupA, p.Asn64Lys | c.2498T > A, p.Met833Lys | |
| 30 | 50/M | 40 | Progressive lower limbs weakness | 2200 | Quadriceps and gastrocnemius (moderate) | Quadriceps weakness (MRC 4) | Ambulant | LGMD | Asymmetry, mild restrictive respiratory involvement (FVC 75%), cardiomyopathy (FE 48%) | c.172C > T, p.Arg58Trp | c.172C > T, p.Arg58Trp |
| 31 | 70/F | 61 | Progressive lower limbs weakness | 2764 | None | Proximal lower limb weakness (MRC 4) | Ambulant | LGMD | Asymmetry | c.191dupA, p.Asn64Lys | c.191dupA, p.Asn64Lys |
| 32 | 42/M | 26 | Distal lower limb weakness | 6182 | Quadriceps (moderate) and gastrocnemius (moderate) | Distal lower limb weakness (MRC 3) | Ambulant | MMD3 | Asymmetry | c.191dupA, p.Asn64Lys | c.191dupA, p.Asn64Lys |
| 33 | 43/M | 34 | Asymptomatic hyperCKemia | 3275 | None | Normal | Ambulant | Hyperckemia | c.191dupA, p.Asn64Lys | c.2190G > T, p.(Trp730Cys) | |
| 34 | 12/F | 4 | Myalgia, exercise intolerance | 3000 | None | Normal | Ambulant | Pseudometabolic | c.191dupA, p.Asn64Lys | c.1359C > G, p.(Tyr453*) | |
MRC, Medical Research Council; LGMD, limb‐girdle muscular dystrophy; MMD3, Miyoshi‐like distal myopathy. Novel variants are represented in bold.