Table 1 |.
Patient summary
| Case No | cDNA (NM_018127.6) | Protein (NP_060597) | Identification | Sex | Age-at-onset | Course | Cardiomyopathy | MRC deficency | Additional clinical features | Previously reported |
|---|---|---|---|---|---|---|---|---|---|---|
| #57415 | c.631C>T; c.1559C>T | p.Arg211∗; p.Thr520Ile | WES | male | 3 months | Unknown | HCM | CI | Psychomotor retardation, mild hypotonia, lactic acidosis, sensorineural hearing impairment, hyperintensities in basal ganglia at age 3 m | Haack et al., 2013 |
| #61982 | c.460T>C; c.460T>C | p.Phe154Leu; p.Phe154Leu | WES | female | 2 months | death at 11 months | HCM | CI | Intrauterine growth retardation, lactic acidosis, cardiac failure; normal muscle biopsy findings | Haack et al., 2013 |
| #65937 | c.1267C>T; c.1267C>T | p.Leu423Phe; p.Leu423Phe | CGS | female | 5 months | death at 4 years and 9 months | HCM | CI | Psychomotor retardation, muscular hypotonia, cardiac failure | Haack et al., 2013 |
| P1 | c.1478C>T; c.202C>T | p.Pro493Leu; p.Arg68Trp | WES | female | Birth | death at 3 weeks | HCM | CI+CIV | Lactic acidosis, muscle weakness, ragged-red fibres and COX-deficient/SDH- hyper-reactive fibres | Taylor et al., 2014 |
| P2 | c.2009del; c.1423+1G>A | p.Cys670Serfs*14; CSM | GP | male | Birth | alive at 8 years | No | ND | Lactic acidosis, developmental delay, ataxia, microcephaly, constipation, cerebellar vermis hypoplasia and prominent posterior fossa on brain MRI | this report |
| P3 | c.297–2_297delinsTG; c.2342G>A | CSM; p.Arg781His | GP | female | 18 months | alive at 5 years | HCM | CI | Elevated blood lactate level (normal serum levels), developmental delay, IUGR | this report |
| P4 | c.2186A>G; c.2342G>A | p.Tyr729Cys; p.Arg781His | WES | female | 2 months | death at 12 weeks | HCM | CI | Lactic acidosis, cardiovascular collapse | this report |
| P5 | c.460T>C; c.460T>C | p.Phe154Leu; p.Phe154Leu | WES | male | neonatal | death at 4 months | HCM | ND | Lactic acidosis, fatal infantile cardiomyopathy | this report |
| P6 | c.798–1G>T; c.1690C>A | CSM; p.Arg564Ser | GP | female | 4 months | death at 5 months | DCM | CI | Lactic acidosis, developmental delay, fatal infantile cardiomyopathy, EF 30% | this report |
| P7 | c.1979A>T; c.2039C>T | p.Lys660Ile; p.Ala680Val | WES | female | 12 months | alive at 24 years | HCM | CI+CIV | Elevated blood lactate level, Patient transplanted at age of 3.8 years | Parikh et al., 2016 |
| P8 | c.245+2T>A; c.1264C>G | CSM; p.Leu422Val | WES | female | 2 months | death at 3 months | DCM | CI | Lactic acidosis, fatal infantile cardiomyopathy, EF 20–30% | this report |
| P9 | c.1163A>G; c.1163A>G | p.Gln388Arg; p.Gln388Arg | GP | male | 6 months | alive at 19 years | HCM | CI | Lactic acidosis, psychomotor retardation, fatigability, peripheral neuropathy | this report |
| P10 | c.457delA; c.2342G>A | p.Ile153Tyrfs*6; p.Arg781His | WES | male | 8 months | alive at 6 years | HCM | CI | Developmental delay, hypotonia, GI dysmotility, s/p cardiac transplant at age of 10 months | Santorelli et al., 2002 |
| P11 | c.460T>C; c.460T>C | p.Phe154Leu; p.Phe154Leu | WES | female | Birth | death at 2.5 months | HCM | CI | Lactic acidosis, later mild muscular hypotonia, lipid storage myopathy on skeletal muscle biopsy | this report |
| P12 | c.297–2_297–1delinsT; c. 2245C>T | CSM; p.His749Tyr | WES | female | 4 months | death at 13 months | HCM | CI+CIV | Lactic acidosis, global developmental delay, hypotonia, s/p cardiac transplant at the age of 10 months | this report |
| P13 | c.460T>C; c.460T>C | p.Phe154Leu; p.Phe154Leu | WES | female | 5 months | death at 5 months | HCM | ND | Lactic acidosis, failure to thrive | this report |
Cases reported by Haack et al., 2013 are indicated in light grey.
MRC - Mitochondrial respiratory chain, WES - whole exome sequencing, GP -gene panel, CGS - candidate gene sequencing CSM - consensus splice mutation; HCM - hypertrophic cardiomyopathy, DCM - dilated cardiomyopathy, CI - Complex I, CIV -Complex IV, ND - not determined