Extended Data Table 1. Clinical table of patients carrying PNPT1 mutations.
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | |||
|---|---|---|---|---|---|---|
| Nucleotide substitutions | c.407G>A hom | c.208T>C het | c.2137G>T het | c.1495G>C het | c.1519G>T het | c.1160A>G hom ref14 |
| Amino acid | p.Arg136His | p.Ser70Pro | p.Asp713Tyr | p.Gly499Arg | p.Ala507Ser | p.Gln387Arg |
| SIFT | Deleterious (score: 0, median: 3.48) | Tolerated (score: 0.1, median: 3.48) | Deleterious (score: 0.01, median: 3.47 | Deleterious (score: 0.0, median: 3.49) | Deleterious (score: 0.0, median: 3.49) | ref14 |
| Mutation Taster | Disease causing (p-value:1) | Disease causing (p-value:0.996) | Disease causing (p-value:1) | Disease causing (p-value:1) | Disease causing (p-value:1) | ref14 |
| Polyphen | Probably damaging with score of 1.0 (sensitivity: 0.0; specificity: 1.0) | Probably damaging with score of 0.588 (sensitivity: 0.81; specificity: 0.83) | Probably damaging with score of 0.998 (sensitivity: 0.18; specificity: 0.98) | Probably damaging with score of 0.994 (sensitivity: 0.46; specificity: 0.96) | Probably damaging with score of 0.913 (sensitivity: 0.69; specificity: 0.90) | ref14 |
| Splicing prediction | Predicted change at 5’ss (-1G>C): -54.0% MaxEnt: -100.0%; NNSPLICE:49.1%: HSF:-12.9% | |||||
| ClinVar | RCV000197606.4 | RCV000033022.3 | ||||
| dbSNP | rs746356243 | - | - | - | - | - |
| gnomAD | 0.0000244 (6 hets /245,972 alleles) | Not recorded (>230,000 alleles) | Not recorded (>230,000 alleles) | Not recorded (>230,000 alleles) | 0.0002241 (62 hets/276,714 alleles) | Not recorded (>230,000 alleles) |
| Clinical features | Intrauterine growth retardation | Truncal hypotonia | Hypotonia | ref14 | ||
| Congenital cataract | Nystagmus | Abnormal eye movements | ||||
| Feeding difficulties | Failure to thrive | Sensory neuropathy | ||||
| Deafness | Sensorineural deafness | Deafness | ||||
| Truncal hypotonia | Hypertonia of the lower limbs | Leucodystrophy | ||||
| Nystagmus | ||||||
| Death at age 2 years | Alive at age 1 years | Alive at age 7 years | Alive at age 13 years | |||
| Brain Imaging | Anomalies of putamen and basal ganglia | Delayed myelination | Delayed myelination; abnormal corpus callosum | ref14 | ||
| Metabolic workup | NMR spectroscopy: lactate peak | NMR spectroscopy: lactate peak | NMR spectroscopy: No lactate elevation | ref14 | ||
| Hyper-lactatemia | Hyper-lactatemia | |||||
| Hyper-lactatorachia | ||||||
| NA | High neopterin in CSF (101 nmol/l) | ND | ND | |||
| Interferon score* (blood analysis) | NA | 4.138 | 2.997 | 2.413 | ||
| RC analysis | Multiple RC deficiency in muscle and fibroblasts | Multiple RC deficiency in fibroblasts | Normal RC activities in fibroblasts | ref14 | ||
het = heterozygous; hets = heterozygotes; hom = homozygous; RC = respiratory chain; NA = not available; ND = not determined; *Normal interferon score value is <2.466. SIFT, Sorting intolerant from tolerant (http://sift.bii.a-star.edu.sg/www/SIFT_aligned_seqs_submit.html)