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All inquiries, additions to the list, and comments should be made to Bill Copeland.
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Amino Acid Substitution: T251I
cDNA Position: 752 c→t (exon 3)
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| Disease | Genetics | Frequency | Reference |
| PEO | ar PEO. Found as compound with R309L, or 2354G insertion, or G848S in PEO. | 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls. | (Ferrari et al., 2005) PubMed |
| PEO | Found in compound with R807P | (Del Bo et al., 2003) PubMed |
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| Infantile Hepatocerebral Syndrome | Frequently found in cis with P587L and compound in trans with L304R, V1106I, and R227W . | Not found in 250 control individuals | (Horvath et al., 2006) PubMed |
| PEO | Found as compound in trans w/ S1176L, G848S, G785X, V1106I, R309L and R227W and cis w/ P587L. Also, T251I/P587L was found as a homozygous mutation. | (Lamantea and Zeviani, 2004) PubMed |
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| PEO and mtDNA deletions | Found in compound w/P587L/ R807P in1 pt. and w/P587L/ H932Y in a 2nd pt. A 3rd pt. was found in compound w/P587L only. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions. | 31 mitochondrial myopathy patients without any family history for the disorder | (Di Fonzo et al., 2003) PubMed |
| Infantile Hepatocerebral Syndrome | 36% of patients with sporadic PEO with multiple mtDNA deletions carry mutations in one of the three genes associated with familial arPEO or adPE. Twinkle gene in 7% and POLG1 gene in 25% of our Italian and British patients with sporadic PEO. Found as co | 7 out of 27patients w/sporadic PEO compared to 250 controls individuals. | (Agostino et al., 2003) PubMed |
| MNGIE | Found in cis with P587L and in trans w/N846S. | Van Goethem, 2003: Not found in 280 control chromosomes | ( Van Goethem et al., 2003c) PubMed |
| Infantile Hepatocerebral Syndrome | Found in 1 of 9 infantile hepatocerebral syndrome patients. In cis with P587L and compound with R232G. | 9 infantile hepatocerebral patients of German and Italian descent. | (Ferrari et al., 2005) PubMed |
| PEO | POLG molecular defects were found in 25% of patients with multiple mtDNA deletions and mitochondrial disease. Found in trans w/M603L and in cis with P587L. | 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. | (Gonzalez - Vioque et al., 2006) PubMed |
| PEO | Found in trans w/ G848S and in cis w/ P587L in a 75 y.o. male. | (Kollberg et al., 2005) PubMed |
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| Alpers | Found in trans w/ G848S and in cis w/ P587L. Also found in cis w/P587L and in trans w/R853Q in myocerebralhepatopathy patient. Also found as a heterozygous mutation with ataxia, ptosis, and neuropathy. | (Wong et al., 2008) PubMed |
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| Alpers | Found in cis w/ R232G and cis w/ P587L. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) PubMed |
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| PEO | Found in cis w/ P587L, with both mutations on each allele. A 2nd pt. found to have P587L in trans and A467T in cis. | (Stewart et al., 2009) PubMed |
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| mtDNA depletion | In cis w/P587L and in trans w/ E1136K | (Taanman et al., 2008) PubMed |
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| Hepatocerebral MDS | Found in cis with P587L and in trans with R232G | (Spinazzola et al., 2009) PubMed |
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| Restless leg syndrome, ptosis, diplopia, limb weakness, blurred vision | Found in trans with P587L. | (Aitken, et al., 2009) PubMed |
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| PEO | Found in trans with W748S andP587L | (Tzoulis, et al., 2009) PubMed |
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| PEO and mental retardation | Found in cis w/P587L and in trans w/ R275X | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| PEO, exercise intolerance, diabetes and a 2nd pt. w/ cataract and myopathy | Found in cis w/P587L and in trans w/ A467T | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Ptosis | Found in cis w/P587L and in trans w/ G848S | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Epilepsy and mental retardation | ad, Found w/P587L | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Seizures, hypotonia, and developmental delay | Found w/P587L | (Burusnukul and de los Reyes, 2009) PubMed |
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| Acute disseminated encephalomyelitis | Found w/P587L, found in one 4 y.o. patient with autoimmune central nervous system disease | (Harris et al., 2010) PubMed |
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| SANDO | Found sporadically w/P587L and G848S in a 80 y.o. male | (Wiess and Saneto, 2010) PubMed |
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| Ptosis and myopathy | Found in cis with P587L and in trans with P648R in a 59 y.o. male with dysphagia, dysphonia, myopathy, ptosis, and mtDNA deletions. Father had same symptoms. | (Ferreira et al., 2011) PubMed |
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| PEO | Found in cis w/ P587L and in trans w/ H932Y in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Peripheral Neuropathy | Found in cis w/ P587L and in trans w/ H932Y in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| PEO | Found in cis w/ P587L and in trans w/ G848S in an 80 y.o. w/ peripheral neuropathy, ptosis, and abnormal muscle histology | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| PEO | Found in cis w/ P587L and in trans w/ K1191N in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weakness | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Found in cis w/ P587L and in trans w/ N1157S in a 9 y.o. Symptoms not noted | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
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| Found in trans w/ G588D and in cis w/ P587L in a 6 y.o. w/ no symptoms noted | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
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| PEO | Found in compound with G848S in a 45 yo female with mtDNA deletions | Found in 160 French cohort of potential POLG patients | (Rouzier et al., 2013) PubMed |
| SANDO | Found in cis with P587L and in trans with A467T in a female in her 60's with a 5 year history of peripheral neuropathy, blurred vision, unstable gait, and sensory ataxia, dementia, and ophthalmoplegia. | (Lovan et al., 2013) PubMed |
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| SANDO | Found in cis w/P587L and in trans w/R869Q in a 34 y.o. female with ataxia, ptosis, diabetes and mtDNA deletions. | (Hanisch et al., 2014) PubMed |
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| PEO | Found in compound w/P587L and D1184N in a 33 y.o. female patient w/ chronic intestinal pseudo-obstruction, PEO, and ataxia. | In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction | (Amiot et al., 2009) PubMed |
| PEO | Found in compound w/P587L and D1184N in a 30 y.o. male patient w/ chronic intestinal pseudo-obstruction and PEO. | In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction | (Amiot et al., 2009) PubMed |
| Found in compound w/ P116Q and P587L in an Italian 8 y.o. female with fatigue,hypotonia, and delayed psychomotor development with no mtDNA depletion. Diabetic father was positive for P116Q and the deaf mother was positive for T251I and P587L. | 0 found in 200 chromosome controls | (Scuderi, et al., 2015) PubMed |
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| Found in compound w/ P116QI andP587L in an Italian 14 y.o. male with fatigue,hypotonia, left eye ptosis, migrains, but normal cognitive skills. Diabetic father was positive for P116Q and the deaf mother was positive for T251I and P587L. | 0 found in 200 chromosome controls | (Scuderi, et al., 2015) PubMed |
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| Parkinsonism and PEO | Found in cis w/P587L and in trans w/W468X. Found in a 68 y.o. female w/ exercise intolerance, PEO, facial diparesis, and left-dominant postural tremor. | (Miguel, et al., 2014) PubMed |
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| PEO | Found in cis with P587L and in trans w/W748S in a 50 y.o.with PEO and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. | (Tzoulis et al., 2016) PubMed |
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| SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) | Found in trans w/G848S and in cis w/P587L with PEO, muscle weakness, and cognitive impairment. Similar to SANDO, but no dysarthria. | (Bereau et al., 2016) PubMed |
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| SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) | Found in trans w/S1095R and in cis w/P587L with PEO, muscle weakness, ataxia, and polyneuropathy. Similar to SANDO, but no dysarthria. | (Bereau et al., 2016) PubMed |
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| SANDO | Found in cis w/P587L and in trans w/R232H and H277L in a 26 y.o. with PEO, cognitive impairment, ataxia, polyneuropathy, msucle weakness, migraines, dysphagia, and dysarthria. | (Bereau et al., 2016) PubMed |
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| PEO | Found in cis with P587L and in trans w/A467T in a 30 y.o. with muscle weaknes and PEO. | (Bereau et al., 2016) PubMed |
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| SANDO | Found in cis w/P587L and in trans w/R232H and H277L in a 40 y.o. with PEO, ataxia, polyneuropathy, and dysarthria. | (Bereau et al., 2016) PubMed |
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| SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) | Found in trans w/R852C and in cis w/P587L in a 50 y.o. with PEO, muscle weakness, and polyneuropathy. Similar to SANDO, but no dysarthria. | (Bereau et al., 2016) PubMed |
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| PEO | Found in trans w/A467T and in cis w/P587L in a 56 y.o. with PEO, muscle weakness, and dysphagia. | (Bereau et al., 2016) PubMed |
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| SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) | Found in trans w/A467T and in cis w/P587L in a 58 y.o. with ataxia, sensory neuropathy, and dysphagia. | (Bereau et al., 2016) PubMed |
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| SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) | Found in trans w/A467T and in cis w/P587L in a 66 y.o. with ataxia, sensory neuropathy, and PEO. | (Bereau et al., 2016) PubMed |
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| PEO | Found in cis w/P587L on both allesls with ptosis and dysphagia | (Bereau et al., 2016) PubMed |
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| SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) | Found in trans w/T251I and P587L with ataxia, sensory neruopathy, PEO, deafness, and dysphagia. | (Bereau et al., 2016) PubMed |
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| PEO | Found in cis with P587L and in trans w/T989dup in a 36 y.o. female with cornieal edema and muscle weakness. One brother affected and has both variants and one unaffected sister with no mutations. | Not found in 100 random controls | (Pozzo et al., 2017) PubMed |
| Neuropathy w/ cataracts and glaucome | Found in trans with R943C and in cis withP587L in an 8 mo. female with uppper and lower limb distal neuromyopathy with ragged red fiberes, cataracts. Later developed ophthalmoparesis, glaucoma, and muscle wasting. | (Castiglioni et al., 2018) PubMed |
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| Neuropathy w/ cataracts and glaucome | Found in trans with R943C and in cis withP587L in an 24 mo. female with uppper and lower limb distal neuromyopathy with ragged red fiberes, cataracts. Later developed ophthalmoparesis, glaucoma, and muscle wasting. | (Castiglioni et al., 2018) PubMed |
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| Late-onset MDS | Found as compound heterozygous in cis with P587L and in trans with R807C in a 70 year-old man presenting with a late onset sensory neuronopathy, chronic progressive external ophthalmoplegia, gait ataxia and parkinsonism. | (Meira et al., 2019) PubMed |
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| MDS | Found in a large cohort study. | (Hikmat et al., 2020) PubMed |
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| Epilepsy | Found in a cross-sectional study of 22676 genetic variants associated with epilepsy | (SoRelle et al., 2020) PubMed |
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