Table 1.
Clinical characteristic and molecular genetic features of nine CMS22 patients
| Feature/Patient | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| PMID | This study | 28,726,805 (IPD1) | 28,726,805 (IPD2) | 28,726,805 (IPD3) | 28,726,805 (IPD4) | 28,726,805 (IPD5) | 24,610,330 | 29,913,539 | 29,483,676 | NA |
| Gender | F | F | F | M | F | M | F | F | F | 7F, 2M |
| Phenotype onset | Neonate | Neonate | Neonate | Neonate | Neonate | Neonate | Neonate | Neonate | Neonate | 9/9 Neonate |
| Age at diagnosis | 6 months | 15 years | 1 years | 2 years | 25 years | 3 years 6 months | NA | NA | 9 years | 6 months−25 years |
| Last evaluated age | 9 months | 17 years | 2 years 5 months | 2 years 10 months | 27 years | 3 years 8 months | 17 months | 3 years | 10 years | 9 months−27 years |
| Failure to thrive | + | + | + | − | − | − | NA | + | + | 5/8 |
| GH deficiency | NA | + | + | + | − | − | + | + | NA | 5/7 |
| PWS/SMA test | SMA (−) | PWS (−) | PWS (−) | PWS (−) | PWS (−) | NA | NA | NA | NA | 5/9 |
| Cystinuria | − | − | − | − | − | + | − | NA | NA | −:6/+:1/NA:2 |
| Neonatal hypotonia | + | + | + | + | + | + | + | + | + | 9/9 |
| Muscular weakness | + | − | + | − | + | + | + | + | + | 7/9 |
| Feeding difficulties | + | + | + | + | + | ‐ | + | + | + | 8/9 |
| Ptosis | − | − | + | + | + | + | + | − | + | 6/9 |
| Walking age | NA | 21 months | 23 months | 22 months | 19 months | 24 months | 17 months | 26 months | 27 months | 17−27 months |
| Childhood‐onset obesity | NA | + | − | − | + | − | NA | NA | + | 3/6 |
| Cognitive/behavioral problems | NA | − | +(DI 69） | + | +(IQ 64） | +(IQ 80） | NA | +(mild) | +(IQ 49） | 6/7 |
|
Pyridostigmine treatment |
Yes, started at 8 months with a positive response | NA | NA | NA | NA | NA | Yes, started at age of 11 weeks with a strongly positive response | Yes, started at 14 months without clinical response | NA | 3/9 |
| Improvement of symptoms (age) | + (9 months) | + (6.5 years) | + (13 months) | + (18 months) | + (1 year) | NA | + (11 weeks) | + (2 years) | + (3 years) | 8/8 |
| Zygosity | Homozygous du to UPD(2)mat | Homozygous | Compound heterozygous | Compound heterozygous | Compound heterozygous | Compound heterozygous | Compound heterozygous | Compound heterozygous | Homozygous | UPD(2)mat:1/Hom:2/Compound Het:6 |
| PREPL mutation | c.1282_1285delTTTG, p.Phe428Argfs*18 | NA | c.358_361delTTTG, p.Val121Ilefs*121 | c.1604T>G, p.Leu535Ter | c.883 C>T, p.Arg295Ter | c.1156−1G>A, p.Leu386_Lys451del | c.807delT, p.Met270Ter | c.1529 + 1G>A; c.1784delinsAA, p.Thr595Lysfs*19 | c.342delA, p.Val115Leufs*39) | Nine different mutations |
| PREPL deletion | NA | PREPL exon 5–10 | PREPL exon 7–8 | SLC3A1 exon10‐PREPL exon10 | PREPL exon12‐CAMKMT exon2 | SLC3A1 exon 7‐CAMKMT exon 2 | SLC3A1 exon5‐PREPL exon9 | NA | NA | Six different deletions |
Abbreviations: +, positive; −, negative; DI, developmental index; IQ, intelligence quotient; Het, heterozygous; Hom, homozygous; F, female; M, male; GH, growth hormone; NA, not applicable.