Table 1.
Clinical and molecular findings in individuals carrying SPEG mutations
| Family-Patient | Gender /age | Genotype | Variant type | Variant location | Isoforms affected |
|---|---|---|---|---|---|
| DCM with no or mild myopathy | |||||
| I-1, I-2 | M/5 years; F/died at 8 months | Homozygous: c.9028_9030delGAG, p.Glu3010del |
In-frame deletion | SK2 | SPEGβ & SPEGα |
| II-1 | F/ 2 years | Homozygous: c.9028_9030delGAG, p.Glu3010del |
In-frame deletion | SK2 | SPEGβ & SPEGα |
| III-1, III-2, III- 3, III-4, III-5 |
M/died between 2 months and 12 years; F/died at 16 years |
Homozygous: c.5038G>A, p.Glu1680Lys | Missense | SK1 | SPEGβ & SPEGα |
| Myopathy with no DCM | |||||
| IV-1 | M/3 years | Homozygous: c.1626_1627insA, p.Thr544fs | Small indel | Between Ig-like 1 and Ig-like 2 |
SPEGβ |
| V-1 | F/10 years | Compound heterozygous: c.1071_1074dup, p.Lys359fs; c.4399C>T, p.Arg1467Ter |
Small indel and nonsense |
Between Ig-like 1 and Ig-like 2; Ig-like 7 |
SPEGβ & SPEGα (partial) |
| VI-1 | F/6.5 years | Compound heterozygous: c.2183delT, p.Leu728fs; c.8962_8963ins25, p.Val2997fs |
Small indels | Ig-like 2; SK2 | SPEGβ & SPEGα (partial) |
| Myopathy and DCM | |||||
| VII-1 | F/died at 3 weeks | Homozygous: c.6697C>T, p.Gln2233Ter | Nonsense | Between SK1 and Ig- like 9 |
SPEGβ &SPEGα |
| VIII-1 | M/died at 19 weeks | Homozygous: c.7119C>A, p.Tyr2373Ter | Nonsense | Between SK1 and Ig- like 9 |
SPEGβ & SPEGα |
| IX-1 | M/8 years | Homozygous: c.9586C>T, p.Arg3196Ter | Nonsense | SK2 | SPEGβ & SPEGα |
| X-1, X-2 | F/died at 3 and 5 days | Homozygous: c.8710A>G, p.Thr2904Ala | Missense | Between Fn type III-2 and SK2 |
SPEGβ & SPEGα |
| XI-1 | M/died at 17 years | Homozygous: c.9185_9187delTGG, p.Val3062del |
In-frame deletion | SK2 | SPEGβ & SPEGα |
| XII-1 | F/6 years | Compound heterozygous: c.3709_3715+29del36, p.Thr1237fs; c.4276C>T, p.Arg1426Ter |
Small indel and nonsense |
Ig-like 6; Ig-like 7 | SPEGβ & SPEGα |
| XIII-1 | M/19 months | Compound heterozygous: c.2915_2916delCCinsA, p.Ala972fs; c.8270G>T, p.Gly2757Val |
Small indel and missense |
Ig-like 4; Fn type III-2 | SPEGβ & SPEGα |
Abbreviations: Ig-like, immunoglobin-like; Fn type III, Fibronectin type III; SK, serine/threonine protein kinase; ASD, atrial septal defect; CHF, congestive heart failure; CM, congenital myopathy; CNM, centronuclear myopathy; DCM, dilated cardiomyopathy; ECG, echocardiogram; LV, left ventricular; LVEF, left ventricular ejection fraction; LVNC, left ventricular non-compaction; LVFS, left ventricular fractional shortening; VSD, ventricular septal defect. SPEGβ (amino acids 1-3267), the longest SPEG isoform and SPEGα (missing amino acids 1-854), the shorter isoform.