Table 2.
Clinical manifestations of HSMR syndrome patients with known deleterious heterozygous CNNM2 mutations
| CNNM2 variants previously reported | CNNM2 variants in novel cohort | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mutation (ref) | p.Ile40SerfsX15 (Stuiver et al., 2011) | p.Ser269Trp (Arjona et al., 2014) | p.Gly357Lys F1 (Arjona et al., 2014) | p.Gly357Lys F2 (Arjona et al., 2014) | p.Thr568Ile (Stuiver et al., 2011) | Del ex1‐4 (F1) | Del ex3‐8 (F2) | p.Leu48Pro (F3) | p.Tyr314X (F4) | p.Leu321del (F5) | p.Val324Met (F6) | p.Leu418Pro (F7) | p.Ser795Leu (F8) | p.Arg797X (F9) | Average |
| Function (% of WT) | 0 | 17 | 1 | 1 | 0 | 0 | 0 | 49 | 12 | 20 | 16 | 46 | 48 | 29 | |
| Serum Mg2+(mmol/L) | 0.51 | 0.44 | 0.56 | 0.5 | 0.6 | 0.63 | 0.57 | 0.45 | 0.48 | 0.5 | 0.54 | 0.49 | 0.72 | 0.57 | 0.54 ± 0.08 |
| Age at onset (year) | 1 | 1 | 0.58 | 0.08 | 16 | 6 | 0.25 | 2 | 3 | 0.67 | 1.08 | 16 | 0.67 | 1 | 3.52 ± 5.50 |
| Obesity (BMI >97th percentile) | N/A | Y | Y | Y | N/A | Y | N | N/A | Y | Y | Y | N/A | N | Y | 80% (8/10) |
| Intellectual disability | N/A | Y | Y | Y | N/A | Y | Y | N | Y | Y | Y | Y | Y | Y | 92% (11/12) |
| Seizures | Y | Y | Y | Y | N | Y | Y | Y | N | Y | Y | Y | N | Y | 79% (11/14) |
| Speech/Communication | N/A | Y | Y | Y | N/A | Y | Y | N | Y | Y | Y | N/A | Y | Y | 91% (10/11) |
| Motor skills defects | N | Y | Y | Y | N | Y | Y | Y | N | Y | Y | N | Y | N | 64% (9/14) |
| Correction by Mg2+ supplementation | N/A | N | N | N | N | N/A | N/A | N | N/A | N | N | N | N | N | 0% (0/10) |
Note: Full correction by Mg2+ supplementation was defined as increasing serum Mg2+ levels to the normal range (0.70–0.05 mmol/L). The average for categorical parameters was determined by (affected probands/total) × 100% of those with available data. Average for continuous parameters are presented as mean ± SD.
Abbreviations: BMI, body mass index; F, family number in Table 1.; N, no; N/A, unknown; WT, wild‐type; Y, yes.