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Table 1 Summary of cases diagnosed via RNA-seq. AE: aberrant expression, AS: aberrant splicing, MAE: mono-allelic expression, Var: intronic variant detected via RNA-seq. Variant coordinates and further details are provided in Additional file 1: Table S1

From: Clinical implementation of RNA sequencing for Mendelian disease diagnostics

Index Patient ID Sex Age range of onset Primary symptoms Genetic diagnosis Variant RNA level Variant class RNA defects
1 R62943 F Prenatal Neurodevelopmental delay, 3-MGA C19orf70 c.143del Frameshift AE, AS
NM_205767.1 c.29+272G>C Intronic  
2 R98254 F Infant Leigh syndrome, basal ganglia abnormality MRI, neurodevelopmental delay, intellectual disability, seizures, encephalopathy, brainstem abnormality MRI, complex I and IV defects MRPL38 c.770C>G Missense AE
NM_032478.3 c.-174_-148del 5′UTR deletion  
3 R86287 M Infant Hypotonia, cardiomyopathy, white matter abnormality MRI, elevated lactate, complex I and IV defects DARS2 c.492+2T>C Splice donor AS
NM_018122.4 c.228-12C>G; c.228-20T>C Intronic multi-nucleotide variant (MNV)  
4 R89912 M Infant Leigh syndrome, basal ganglia abnormality MRI, neurodevelopmental delay, speech delay, intellectual disability, encephalopathy, hypotonia, nystagmus, brainstem abnormality MRI, elevated lactate, metabolic acidosis, complex I defect NFU1 c.362T>C Missense AE, MAE
NM_001002755.2 c.485-2588_545+1655del Deletion  
5 R19100 M Child Myopathic facies, exercise intolerance, muscle weakness, motor, growth, speech and neurodevelopmental delay, intellectual disability, microcephaly, hypotonia, cardiomyopathy, dysmorphic features, ragged red fibers, elevated lactate SLC25A4 c.598G>A Splice region AE
NM_001151.3 c.598G>A Splice region  
6 R15264 F Infant Muscle weakness, myopathy, muscular dystrophy, hypotonia TIMMDC1 c.596+2146A>G Intronic AE, AS, Var
NM_016589.3 c.596+2146A>G Intronic  
7 R36605 M Infant Acute liver failure, hypotension of the muscles, hypertension of the limbs, intermittent deficiency of motor function of the pupil, delayed light reaction and nystagmus TWNK c.1302C>G Synonymous AE, AS
NM_001163812.1 c.1302C>G Synonymous  
8 R61100 F Infant Encephalopathy, respiratory distress NAXE c.292-12C>G Intron AE, AS
NM_144772.2 c.292-12C>G Intron  
9 R77611 F Infant Recurrent acute liver failure DLD c.685G>T Missense AE, MAE
NM_000108.3    
10 R16472 M Child Motor developmental delay, neurodevelopmental delay, respiratory distress, brainstem abnormality MRI, white matter abnormality MRI, leukoencephalopathy, elevated lactate, complex IV defect MRPS25 c.329+75G>A Intronic AE, AS, Var
NM_022497.4 c.329+75G>A Intronic  
11 R51757 M Infant Motor developmental delay, neurodevelopmental delay, seizures, feeding difficulties, elevated lactate, complex I defect NDUFA10 c.-99_-75del 5′UTR AE
NM_004544.3 c.-99_-75del 5′UTR  
12 R80346 F Birth MDDS, seizures, encephalopathy, hypotonia, died as neonate, elevated lactate, complex III, IV and V defects LIG3 c.86G>A Stop AE, Var
NM_002311.4 c.1611+208G>A Intronic  
13 R20754 M Neonatal Nystagmus, hearing impairment, white matter abnormality MRI UFM1 c.-273_-271del Promoter AE
NM_016617.2 c.-273_-271del Promoter  
14 R25473 F Adult Usher syndrome, immune abnormality, neutropenia, abnormality retina, cataract, visual impairment, hearing impairment PEX1 c.1842del Frameshift AE, Var
NM_000466.2 c.1240-1551A>G Intronic  
15 R28774 M Infant Myopathy, neurodevelopmental delay, hypotonia, movement disorder, failure to thrive, feeding difficulties, died as a young child due to recurrent respiratory infections, complex I defect TIMMDC1 c.596+2146A>G Intronic AE, AS, Var
NM_016589.3 c.596+2146A>G Intronic  
16 R96820 F Neonatal Muscle weakness, neurodevelopmental delay, hypotonia, microcephaly, cardiomyopathy, hearing impairment, elevated lactate, metabolic acidosis, complex IV defect CLPP c.661G>A Splice region AE, AS
NM_006012.2 c.661G>A Splice region  
17 R21147 M Infant Neurodevelopmental delay, feeding difficulties, elevated lactate, complex I defect NDUFA10 c.-99_-75del 5′UTR AE
NM_004544.3 c.-99_-75del 5′UTR  
18 R64921 M Child Ophthalmoplegia, speech delay, developmental regression, ataxia, abnormality retina, visual impairment, complex I defect MCOLN1 c.681-19A>C Intronic AE, AS
NM_020533.2 c.832C>T Stop  
19 R52016 M Infant Died as infant, basal ganglia abnormality MRI, neurodevelopmental delay, encephalopathy, hypotonia, myoclonus, nystagmus, abnormality eye movement, neuropathy, brainstem abnormality MRI, elevated lactate, complex I defect TIMMDC1 c.596+2146A>G Intronic AE, AS, Var
NM_016589.3 c.596+2146A>G Intronic  
20 R46723 F Infant Basal ganglia abnormality MRI, encephalopathy, brainstem abnormality MRI, complex I defect NDUFAF5 c.2T>C Start loss AE, AS, Var
NM_024120.4 c.223-907A>C Intronic  
21 R58859 M Adult Ophthalmoplegia, myopathic facies, myalgia, diabetes, arrhythmias TAZ c.348C>T Synonymous AS
NM_181313 c.348C>T Synonymous  
22 R80184 M Prenatal Muscle weakness, myopathy, neurodevelopmental delay, intellectual disability, seizures, hypotonia, dystonia, spasticity, microcephaly, growth delay, failure to thrive, respiratory distress, cataract, abnormality eye movement, delayed myelination, hypoplasia of the corpus callosum, lack of insular opercularization, died as a young child from pneumonia, elevated lactate, complex I and I/III defects ALDH18A1 c.1982C>A Stop AE, MAE
NM_001017423.1 c.1858C>T Missense  
23 R59185 F Child Basal ganglia abnormality MRI, ophthalmoplegia, ataxia, growth delay, arrhythmias, optic atrophy, visual impairment, neuropathy, white matter abnormality MRI, elevated lactate NDUFS4 c.466_469dup Frameshift AE
NM_002495.2 c.466_469dup Frameshift  
24 R63087 M Child Basal ganglia abnormality MRI, muscle weakness, myopathy, rhabdomyolysis, neurodevelopmental delay, seizures, infection related deterioration, elevated lactate SLC25A42 c.380+2T>A Splice donor AS
NM_178526.4 c.380+2T>A Splice donor  
25 R44456 F Infant MADD, respiratory distress, dysmorphic features MRPL44 c.179+3A>G Splice region AE, AS
NM_022915.3 c.179+3A>G Splice region  
26 R33391 F Infant Failure to thrive, elevated lactate, complex I defect NDUFAF5 c.605dup Frameshift AS, Var
NM_024120.4 c.223-907A>C Intronic  
27 R66696 M Young child Muscle weakness, myopathy, rhabdomyolysis, infection related deterioration, died as child, complex I, III and IV defects LPIN1 c.2550-865_2667-34del Deletion AS
NM_001261427.1 c.2550-865_2667-34del Deletion  
28 R24289 M Young child Hypotonia, developmental delay, hearing impairment, white matter abnormality on MRI, lactic acidemia, hyperlactacidemia, proteinuria, glycosuria RRM2B c.328C>T Missense AE, MAE
NM_015713.4 c.? Intergenic  
29 R98349 F Infant Clotting defect, lactic acidosis DLD c.685G>T Missense AS
NM_000108.5 c.1046+5G>T Splice region  
30 R91273 F Adult MADD during pregnancy ETFDH c.687_688del Frameshift AE
NM_004453.3 -   
31 R60537 M Neonatal Congenital disorder of glycosylation, seizures, cognitive impairment, nose abnormalities, large fleshy ears, abnormal isoelectric focusing of serum transferrin ATP6AP1 c.291-135C>T Intronic AE, Var
NM_00183.4 c.291-135C>T Intronic  
32 R70961 M Young child Leigh syndrome, optic atrophy, parkinsonism, status epilepticus, developmental regression, abnormal thalamic size, lactic acidosis, urinary glycosaminoglycan excretion PTCD3 c.1519-1G>C Splice acceptor AS
NM_017952 c.1918C>G Missense