Table 1.
Human genetic diseases linked to mCa2+ handling proteins
| Reference | Genetic Defect | Disease/Major Phenotype(s) |
|---|---|---|
| Logan et al. (199) | Loss of function mutations in MICU1 | Excessive mCa2+ uptake, proximal myopathy, learning defects, and a progressive extrapyramidal movement disorder |
| Lewis-Smith et al. (200) | Homozygous, 2,755-bp deletion in MICU1 | Lethargy, fatigue, and muscle weakness presenting in childhood |
| O’Grady et al. (201) | Loss of function mutation in MICU1 | Congenital muscular dystrophy |
| Musa et al. (202) | Homozygous c.553C>T (p.Q185*) mutation in MICU1; predicted to cause complete loss of protein function | Muscle weakness, fatigue; in some instances accompanied by extrapyramidal signs, learning disability, nystagmus, and cataracts |
| Mojbafan et al. (203) | C1295delA mutation in exon 13 of MICU1, causing a frameshift and protein truncation | Myopathy with extrapyramidal signs |
| Wilton et al. (573) | Two distinct heterozygous MICU1 mutations in the same patient, one on the maternal allele and one on the paternal allele: • c.161 + 1G>A in MICU1, likely disrupting splicing and gene function • c.386G>C in MICU1, resulting in R129P missense mutation |
Myopathy with extrapyramidal signs, also acute encephalopathy and developmental brain abnormalities |
| Shamseldin et al. (233) | Homozygous c.42G>A:P.W14* mutation in MICU2, causing an early stop codon and protein truncation | Neurodevelopmental disorder with severe cognitive impairment, spasticity, and white matter involvement. Patient fibroblasts have excessive mCa2+ uptake. |
| Endele et al. (341) | Deletion of regions of the short arm of chromosome 4 (4p16.3), including LETM1 | Wolf–Hirschhorn syndrome: impaired growth, developmental delay, microcephaly, and mental defects. Sometimes involves impaired muscle tone, seizures, and congenital heart defects. |
| South et al. (371) | Microdeletion in 4p16.3, including LETM1 | Developmental delays and delayed growth, unique facial features distinct from those of Wolf–Hirschhorn syndrome; variable involvement of seizures |
| Cyr et al. (375) | Microduplication of 4p16.3, including LETM1 | Macrocephaly, normal growth, irregular iris pigmentation, delayed development, dysmorphic features, and seizures |
| Roselló et al. (376) | Submicroscopic duplication in 4p16.2, including LETM1 | Phenotype intermediate between Wolf–Hirschhorn syndrome and 4p trisomy; facial dysmorphism, delayed gross motor development |
See glossary for abbreviations.