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53 patient data entries in database for mutation P587L. Entry
# | | Mutations | | allele 1 | allele 2 |
| Clinical representation | Symptoms | Age group | Age of onset | Age of patient | Age of death | Reference | | | 11 | T251I
P587L2
| C224Y4
| Alpers, trunk hypotonia, seizures at 4 months, RC deficiency in liver. 28% mtDNA copy number in liver. | | | 0.3 | n/a | n/a | Sarzi et al, 2007; [view data] | | 12 | T251I
P587L2
| R227W4
| PEO | | | 48 | n/a | n/a | Horvath et al, 2006; [view data] | | 19 | T251I
P587L2
| R232G4
| Alpers, epilepsy and hepatopathy, onset 5 months of age. | | | 0.5 | n/a | n/a | Ashley et al, 2008; [view data] | | 23 | T251I
P587L2
| T251I
P587L2
| PEO with myopathy, chronic bronchitis. | | | 63 | n/a | n/a | Horvath et al, 2006; [view data] | | 24 | N864S1
| T251I
P587L2
| MNGIE-like, presented with GI symptoms, ptosis, neuropathy, muscle weakness. | | | 15 | n/a | n/a | Van Goethem et al, 2003c; [view data] | | 25 | H932Y1
| T251I
P587L2
| Peripheral neuropathy, exercise intolerance, muscle cramps after exercise, easy fatigability, arrythmia, CPEO, abnormal EMG/NCV, ptosis, cataract, abnormal muscle histology, abnormal muscle ultrastructure, COX deficiency, ragged red fibers. 123% mtDNA copy number in blood. | | - | abnormal muscle histology | |
| - | abnormal muscle ultrastructure | |
| | n/a | 31 | n/a | Tang et al, 2011; [view data] | | 26 | H932Y1
| T251I
P587L2
| Peripheral neuropathy, ptosis, muscle weakness, CPK abnormalities. 77% mtDNA copy number in blood. | | | n/a | 41 | n/a | Tang et al, 2011; [view data] | | 27 | G848S1
| T251I
P587L2
| Ocular bulbar weakness, peripheral neuropathy, muscle weakness, CPEO, ptosis, hypothyroidism, abnormal muscle histology, abnormal muscle ultrastructure, large mitochondrial proliferation, ragged red fibers. 96% mtDNA copy number in blood. Patient II-44. | | - | abnormal muscle histology | |
| - | abnormal muscle ultrastructure | |
| | n/a | 81 | n/a | Tang et al, 2011; [view data] | | 28 | K1191N1
| T251I
P587L2
| Stroke/ischaemic episodes, peripheral neuropathy, CPEO, abnormal EMG/NCV, ptosis, muscle weakness, headache/migraine. 167% mtDNA copy number in blood. | | | n/a | 39 | n/a | Tang et al, 2011; [view data] | | 29 | K1191R1
| T251I
P587L2
| Developmental delay/dementia, liver dysfunction, lactic acidosis, fatigue, pancreatitis, cyclic vomiting. | | | 1 | n/a | n/a | Wong et al, 2008; [view data] | | 30 | V1106I1
| T251I
P587L2
| PEO with myopathy | | | n/a | 35 | n/a | Horvath et al, 2006; [view data] | | 31 | E1136K1
| T251I
P587L2
| Vomiting, FTT, hypotonic, lactic acidemia, hypoglycemia, bilateral dense cataracts, hepatomegaly, jaundice, septicemia. infantile hepatocerebral mtDNA depletion. Mother with E1136K allele reported as asymptomatic. Father with T251I/P587L allele reported as asymptomatic. | | | 0.01 | n/a | 0.5 | Taanman et al, 2009; [view data] | | 33 | R232G4
| T251I
P587L2
| Infantile hepatocerebral, presented at 3 months as hypotonia followed by mtDNA depletion in liver, dementia, and death at 6 months by ventilatory insufficiency. | | | 0.3 | n/a | 0.5 | Ferrari et al, 2005; [view data] | | 35 | W748S5
| T251I
P587L2
| PEO, ptosis, muscle fatigue, diplopia, a mild external ophthalmoplegia affecting horizontal, but not vertical gaze. Tendonreflexes were diminished in the lower extremities and a distal sensory defect in stocking distribution was seen. | | - | external ophthalmoplegia | |
| | 45 | 50 | n/a | Tzoulis et al, 2009; [view data] | | 36 | M603L2
| T251I
P587L2
| PEO with ptosis, mild atrial hypertrophy. Sister had PEO. | | | 61 | 65 | n/a | Gonzalez-Vioque et al, 2006; [view data] | | 37 | T251I
P587L2
| T251I
P587L2
| PEO with myopathy | | | 62 | 70 | n/a | Horvath et al, 2006; [view data] | | 38 | T251I
P587L2
| T251I
P587L2
| PEO with myopathy | | | n/a | 56 | n/a | Horvath et al, 2006; [view data] | | 39 | T251I
P587L2
| T251I
P587L2
| Mild bilateral ptosis, PEO. | | | 41 | n/a | n/a | Stewart et al, 2009; [view data] | | 40 | A467T2
| T251I
P587L2
| PEO, ptosis, proximal weakness, multiple mtDNA deletions-LPCR. 25% COX-deficient fibers | | | 45 | n/a | n/a | Stewart et al, 2009; [view data] | | 41 | A467T2
| T251I
P587L2
| Exercise intolerance, CPEO, retinitis pigmentosa, diabetes, limb girdle weakness. 2nd patient with cataract and myopathy | | | n/a | 51 | n/a | Blok et al, 2009; [view data] | | 42 | L304R3
| T251I
P587L2
| PEO, myopathy, ataxia. | | - | movement disorder (ataxia) | |
| | 45 | 74 | n/a | Horvath et al, 2006; [view data] | | 43 | L304R3
| T251I
P587L2
| PEO, Neuropathy. Affect sibling. | | | 60 | 68 | n/a | Horvath et al, 2006; [view data] | | 44 | P648R5
| T251I
P587L2
| Ptosis, oculopharyngeal muscular dystrophy-like, pigmentary retinopathy. | | | 59 | 67 | n/a | Ferreira et al, 2011; [view data] | | 45 | R807P3
| T251I
P587L2
| PEO | | | 46 | 47 | n/a | Di Fonzo et al, 2003; [view data] | | 46 | R807P3
| T251I
P587L2
| PEO, dysphagia | | | 45 | 52 | n/a | Di Fonzo et al, 2003; [view data] | | 47 | R807P3
| T251I
P587L2
| PEO, axonal sensorimotor polyneuropathy | | - | axonal sensorimotor polyneuropathy | |
| | 60 | 71 | n/a | Di Fonzo et al, 2003; [view data] | | 48 | N1157S1
| T251I
P587L2
| N/A (as reported in Tang 2011 JMG) | | | n/a | 9 | n/a | Tang et al, 2011; [view data] | | 49 | R853Q1
| T251I
P587L2
| Developmental delay, dementia, lactic acidosis, microcephaly, FTT, hearing loss, abnormal MRI. | | | n/a | 0.2 | n/a | Wong et al, 2008; [view data] | | 137 | W748S5
| P587L2
P589L2
| Encephalopathy onset 16 years of age, presented with epilepsy. | | | 16 | n/a | n/a | Ashley et al, 2008; [view data] | | 250 | G848S1
| T251I
P587L2
| PEO, severe ophthalmoplegia and ptosis, which appeared insidiously and had been present clinically since the age of 55. Muscle biopsy at age 68 revealed mitochondrial myopathy, as well as muscle inflammation with granulomas. multiple mtDNA deletions in muscle tissue. | | | 55 | 75 | n/a | Kollberg et al, 2005; [view data] | | 263 | R227W4
| T251I
P587L2
| PEO, bilateral ptosis, severe limita- tion of ocular motility, and a mosaic distribution of ragged-red and cytochrome c oxidase–negative fibers in the muscle biopsy. All patients had multiple deletions of muscle mtDNA. | | | 48 | n/a | n/a | Agostino et al, 2003; [view data] | | 283 | | T251I
P587L2
| Global developmental delay, Central hypotonia, Torticollis, feeding difficulty at birth, myoclonic seizure, horizontal nystagmus, Intermittent estropia, Abnormal MRI | | | 0.4 | n/a | n/a | Burusnukul and de los Reyes, 2009; [view data] | | 284 | K1191R1
| T251I
P587L2
| Presented with feeding difficulties and hypotonia, At 4.5 months of age the patient contracted an influenza A infection. Concurrently she experienced hepatomegaly associated with severe hypoglycemia, Abnormalities in liver synthetic function, elevations in liver hepatocellular enzymes, elevated cerebrospinal fluid (CSF) protein, severely reduced mtDNA (3%) in liver. liver failure. She showed signs of ongoing respiratory difficulty, pancreatitis, and renal tubulopathy | | | 0.166 | 0.416 | 0.458 | Lutz et al, 2009; [view data] | | 313 | G848S1
| T251I
P587L2
| progressively droopy eyelids, double vision, gait instability, proximal arm weakness, ragged red and ragged blue (succinate dehydrogenase–positive) fibers in about 3% and 6% of all muscle fibers, bilateral ptosis, diplopia, dysarthria, myopathy involving the facial muscles, sensory ataxic polyneuropathy | | | n/a | 80 | n/a | Weiss and Saneto, 2010; [view data] | | 421 | D1184N1
| T251I
P587L2
| Peripheral neuropathy, PEO, ataxia, epilepsy, fatty liver | | - | movement disorder (ataxia) | |
| | 9 | n/a | 33 | Amiot et al, 2009; [view data] | | 422 | D1184N1
| T251I
P587L2
| Peripheral neuropathy, PEO, fatty liver | | | 9 | n/a | 30 | Amiot et al, 2009; [view data] | | 475 | | T251I
P587L2
| Progressively blurred vision, diplopia, and longstanding bilateral ptosis (adPEO). She described occasional choking episodes after eating as well as fatigue and shortness of breath after minimal exertion. Lower limb examination revealed symmetric proximal limb weakness with reduced reflexes and flexor plantars. Tan- dem gait was hesitant. The initial differential diagnosis included Graves thyroid eye disease, a neuromuscular junction disor- der (myasthenia gravis or botulism), oculopharyngeal muscular dystrophy, Miller Fisher variant of Guillain-Barre syndrome, and progressive muscular dystrophy. Borderline myopathy. The muscle biopsy showed 13% cytochrome c ox- idase (COX)–deficient fibers, significant numbers of ragged red fibers but no excess of lipid or glycogen accumulation, and subsarcolemmal accumulation of abnormal mitochondria suggestive of a mitochondrial cytopathy. The patient presented 10 months later with an un- pleasant “jumping†sensation in her feet when at rest which was relieved by movement. Symptoms were worse at night and she also described sudden involuntary movements of her lower limbs (restless legs syndrome, RLS). | | | 53 | 58 | n/a | Aitken et al, 2009; [view data] | | 503 | R869Q1
| P587L2
T251I
| Pareses, ptosis, ataxia, sensory neoropathy, motor neuropathy, axonal neuropathy, demyelinating neuropathy. | | - | movement disorder (ataxia) | |
| - | demyelinating neuropathy | |
| | 29 | 34 | n/a | Hanisch et al, 2014; [view data] | | 508 | | T251I
P587L2
| Progressive ataxia, asymmetrical right ophthalmoplegia and encephalopathy. Seizures. Loss of extraocular movement on the right and right arm and leg spasticity and hyperreflexia. Elevated lactate level, a markedly depressed N-acetylaspartate level, and a markedly elevated choline level. Steroid-induced hyperglycemia. Progressive acute disseminated encephalomyelitis (ADEM). | | - | movement disorder (ataxia) | |
| | n/a | 4 | 4.75 | Harris et al, 2010; [view data] | | 530 | P116Q
| T251I
P587L2
| He presented migraine by age 7 and complained of fatigue during exercise by age 12. mild diffuse muscle hypotonia and flat feet. ptosis at 14. Brain MRI showed mild white matter hyperintensity. | | | 7 | 14 | n/a | Scuderi et al, 2015; [view data] | | 531 | P116Q
| T251I
P587L2
| delayed psychomotor development. At age 3, neurological examination showed muscular hypotonia, joint laxity, absent deep tendon reflexes, broadbased gait, scapular winging, accentuation of lumbar lordosis and flat feet. intellectual disability. progressive cognitive impairment. mild myopathy. | | | 3 | 8 | n/a | Scuderi et al, 2015; [view data] | | 532 | | T251I
P587L2
| leg pain after physical activity. mild diffuse muscle hypotonia, hypotrophy, mild diffuse muscle weakness, joint laxity, scapular winging and increase of lumbar lordosis. Borderline intellectual functioning. | | | n/a | 10 | n/a | Scuderi et al, 2015; [view data] | | 533 | | T251I
P587L2
| Presented deafness from childhood. migraine and fatigue. On neurological examination she had mild diffuse muscle weakness. Audiometric examination disclosed neurosensorial hypoacusia. mild anxiety with specific phobias concerning indoor environment and crowd. | | | 29 | 37 | n/a | Scuderi et al, 2015; [view data] | | 584 | W748S5
E1142G
| T251I
P587L2
| Akinetic-rigid Parkinsons. impaired balance, freezing, and increased salivation. Constipation and muscle cramps. He had arterial hypertension and mild normocytic anemia. cytochrome c oxidase-negative muscle fibers. | | | 49 | 65 | n/a | Ylönen et al, 2013; [view data] | | 588 | T251I
P587L2
| T251I
P587L2
| Alpers. nocturnal nausea followed by loss of consciousness without motor relinquishing. obsessive–compulsive disorder. | | | 16 | 26 | n/a | Stewart et al, 2011; [view data] | | 600 | Nonsense
mutation:
R709X
| T251I
P587L2
| PEO, complicated by dysphagia, myopathy. | | | n/a | 52 | n/a | Del Bo et al, 2003; [view data] | | 601 | R807P3
| T251I
P587L2
| PEO, complicated by dysphagia, myopathy. | | | n/a | 71 | n/a | Del Bo et al, 2003; [view data] | | 603 | R309L3
| T251I
P587L2
| PEO. cytochrome c oxidase negative ragged red fibers, and multiple mtDNA deletions in skeletal muscle. | | | n/a | n/a | n/a | Lamantea et al, 2002; [view data] | | 604 | G848S1
| T251I
P587L2
| PEO. cytochrome c oxidase negative ragged red fibers, and multiple mtDNA deletions in skeletal muscle. | | | n/a | n/a | n/a | Lamantea et al, 2002; [view data] | | 605 | Frameshift:
G785fs
| T251I
P587L2
| PEO. cytochrome c oxidase negative ragged red fibers, and multiple mtDNA deletions in skeletal muscle. | | | n/a | n/a | n/a | Lamantea et al, 2002; [view data] | | 618 | A467T2
| T251I
P587L2
| diabetes mellitus 2, congestive heart failure, hypothyroidism, hypertension, depression with psychotic features and gastric bypass surgery. gait difficulties, cognitive impairment, ophthalmoplegia, resting tremor and peripheral neuropathy. Shooting pains and numbness in her lower extremities, occasional rectal incontinence. Presyncopal dizziness. Complicated diabetic retinopathy. sensory ataxia secondary to a sensorimotor polyneuropathy, chronic supranuclear ophthalmoplegia, and a resting tremor of her right hand. bilateral ptosis and marked temporal muscle wasting. Her sensory examination found loss of pinprick sensation, temperature and vibration bilaterally up to her hips. She had bilateral vibration loss at her fingertips. She had loss of proprioception at her toes. She had bilateral dysdiadochokinesia with significant ataxia on finger to nose testing. Arreflexic in her lower extremities. On cognitive testing she was found to have moderate dementia with significant deficits in registration and construction as well as ideomotor apraxia. | | - | movement disorder (ataxia) | |
| - | axonal sensorimotor polyneuropathy | |
| | 55 | 60 | n/a | Lovan et al, 2013; [view data] | | 639 | G848S1
| T251I
P587L2
| Alpers | | | 0.5 | n/a | n/a | Wong et al, 2008; [view data] | | 695 | Nonsense
mutation:
W486X
| T251I
P587L2
| slowly progressive bilateral blepharoptosis, severe PEO, dysphagia, facial diparesis and exercise intolerance, presented, at the age of 60, with left-dominant postural tremor, reduced left arm swing during gait, postural instability, axonal sensory polyneuropathy, CT showed diffuse cerebral atrophy. Parkinsons. | | | 46 | 66 | n/a | Miguel et al, 2014; [view data] |
1-5 pathogenic cluster assignment of mutations. Mutations displayed without a superscript number are outside of the assigned pathogenic clusters. See cluster definitions for details. Number of displayed patient cases: 53
Number of patient cases marked as outliers: 2 (cases excluded from avg: 283, 508)
Avg age of onset in displayed cases: 35.0
Std dev in onset in displayed cases: 24.2
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