|
68 patient data entries in database for cluster 1. Entry
# | | Mutations | | allele 1 | allele 2 |
| Clinical representation | Symptoms | Age group | Age of onset | Age of patient | Age of death | Reference | | | 181 | Y831C
| H1134R1
| Anorexia, FTT, drowsiness, hepatomegaly, peripheral odema, liver failure. Onset at 3 months with infantile hepatocerebral mtDNA depletion. Death at 6 months. Asymptomatic mother and father. | | | 0.3 | n/a | 0.5 | Taanman et al, 2009; [view data] | | 528 | | R1187W1
| Mitochondrial depletion syndrome and T cell immunodeficiency. severe recurrent infectious diseases, anemia, and thrombocytopenia. Clinically, he presented with severe psychomotor retardation, axial hypotonia, and a disturbed pain perception leading to debilitating biting of the thumb, lower lip, and tongue. Brain imaging showed hypoplasia of corpus callosum and an impaired myelinization of the temporo- occipital region with consecutive supratentorial hydrocephalus. MtDNA depletion. Neurologic examination revealed adynamia, hypotonia of the trunk, complete absence of deep tendon reflexes as well as primitive reflexes, and a disturbed pain perception with complete absence of pain expression. axonal and demyelinating neuropathy. septicemia with maculopapular exanthema, paronychia, and conjunctivitis. | | - | demyelinating neuropathy | |
| | 0.01 | n/a | 1.33 | Reichenbach et al, 2006; [view data] | | 405 | | A143V1
| Onset with seizures at 6 months, alpers syndrome. Muscle mtDNA depletion. | | | 0.5 | n/a | 2 | Sarzi et al, 2007; [view data] | | 208 | | Y955C1
| Onset 0.1 years with dementia, liver dysfunction, lactic acidosis, hearing loss, failure to thrive, generalized ETC complex deficiency. | | | 0.1 | n/a | n/a | Wong et al, 2008; [view data] | | 196 | | E895G1
| Found in one newborn with floppiness and 20% liver mtDNA depletion- Myopathic MDS. Death at 36 hours after birth. 5% mtDNA copy number in muscle, 20% mtDNA copy number in liver. | | | 0.01 | n/a | 0.02 | Spinazzola et al, 2009; [view data] | | 2 | D136E1
| Q45R
| Epilepsy. Father was heterozygous Q45R and epileptic, Mother was heterozygous D136E and had no symptoms. | | | n/a | 4 | n/a | Blok et al, 2009; [view data] | | 643 | | V855A1
| Muscle weakness, PEO | | | 9 | n/a | n/a | Wong et al, 2008; [view data] | | 485 | | Y955C1
| Resting tremor, rigidity, bradykinesia, ptosis, PEO, muscle weakness, periodic depression, dementia, cataracts, Parkinsons. | | | 10 | 58 | 65 | Luoma et al, 2004; [view data] | | 251 | A889T1
E1143G
| | presented at age 7 years with gait difficulty and pes cavus. He developed upper extremity tremor, scanning speech, and horizontal nystagmus by age 15. at age 20 showed ptosis, external ophthalmoplegia, mildly decreased vibration and pin prick sensation, intention tremor, absent ankle and brachioradialis reflexes, and ataxic gait. Over the next 5 years, he experienced progression of the ptosis and ophthalmoplegia. The tremor became disabling at rest and with action, and he became wheelchair-dependent. | | - | movement disorder (ataxia) | |
| - | external ophthalmoplegia | |
| | 7 | 20 | n/a | Hisama et al, 2005; [view data] | | 431 | | R1187W1
| Hepatic failure, myopathy, psychomotor delay. 14-year-old boy born of healthy consanguineous parents. He presented delayed psychomotor development and mus- cular weakness associated with hepatopathy. He had recurrent episodes of cholestasis and cytolysis and liver biopsy showed fibrosis and severe steatosis. He was heterozygous for the p.Arg1187Trp mutation, previously identified in a patient with mitochondrial depletion syndrome and T-cell immunodeficiency. | | | 14 | n/a | n/a | Rouzier et al, 2013; [view data] | | 335 | | Y951N1
| bilateral cataracts, ovarian dysgenesis and distal muscle weakness and atrophy, progressive muscle weakness, seizure like episode, atrophy of arm and hand muscles, | | | 18 | 23 | n/a | Bekheirnia et al, 2012; [view data] | | 495 | | Y955C1
| Parkinsons, resting tremor, ptosis, PEO, Muscle weakness, cataracts, Neuropathy | | | 30 | 74 | n/a | Luoma et al, 2004; [view data] | | 526 | | Y955C1
| rigidity with cogwheel phenomenon, bradykinesia, resting tremor and postural instability. Ragged-red fibers as well as fibers with increased subsarcolemmal succinate dehydrogenase activity and decreased cytochrome c oxidase activity. Multiple mtDNA deletions were detected. Parkinsons. PEO. | | | 60 | 73 | n/a | Mukai et al, 2013; [view data] | | 525 | | Y955C1
| gait instability, mild parkinsonian features, including cogwheel rigidity and bradykinesia. ragged-red fibers, decreased cytochrome c oxidase activity. Multiple mtDNA deletions were detected. PEO. | | | 65 | 69 | n/a | Mukai et al, 2013; [view data] | | 519 | | R852C1
G11D
| progressive cerebellar syndrome, slurred speech, balance disturbances, mild incoordination, type II diabetes mellitus, dysarthria, mild limb dysmetria, mildly impaired tandem gait, cerebellar ataxia. She had polyminimyoclonus of her outstretched hands, a positive glabellar tap and brisk deep tendon reflexes with flexor plantar responses. She had Rigidity in the legs worse than in the arms, brisk reflexes, and mild bilateral bradykinesia in association with dystonic posturing of the left hand. Dystonia. | | - | movement disorder (ataxia) | |
| | 49 | 58 | n/a | Mehta et al, 2011; [view data] | | 518 | D1184H1
| S998L
| bilateral ptosis and external ophthalmoplegia at 64 years of age. at 67 years she was severely cognitively impaired, had severe bilateral ptosis and complete external ophthalmoplegia. Frequent cytochromecoxidase-negative fibres were detected in muscle. Electrophysiological examination revealed myopathic changes and axonal neuropathy. PEO, progressive encephalopathy. | | - | demyelinating neuropathy | |
| - | external ophthalmoplegia | |
| | 64 | 67 | n/a | Martikainen et al, 2010; [view data] | | 502 | H932Y1
| R386C
| Isolated distal myopathy of the upper extremities, cytochrome c oxidase deficient fibers, muscle weakness. mtDNA depletion. Reduced Deep tendon reflexes in the upper extremities. | | | 24 | 27 | n/a | Giordano et al, 2010; [view data] | | 501 | | A1105T1
| PEO, premature menopause, Parkinsons, resting tremor, bradykinesia, ptosis, muscle weakness, cataracts, goitre, head tremor. | | | 42 | 75 | n/a | Luoma et al, 2004; [view data] | | 500 | | R953C1
| PEO, ptosis, muscle weakness, hypothyreosis, ataxia, asthma, balance disturbance. | | - | movement disorder (ataxia) | |
| | 22 | 29 | n/a | Luoma et al, 2004; [view data] | | 499 | | Y955C1
| PEO, premature menupause, ptosis, muscle weakness, cataracts | | | 30 | 52 | n/a | Luoma et al, 2004; [view data] | | 498 | | Y955C1
| PEO, ptosis, cataracts, rheumatoid arthritis, cardiac failure | | | 40 | n/a | 67 | Luoma et al, 2004; [view data] | | 497 | | Y955C1
| Ptosis, PEO, Exercise intolerance, pigmentary retinopathy, neuropathy | | | 28 | 30 | n/a | Luoma et al, 2004; [view data] | | 496 | | Y955C1
| Parkinsons, resting tremor, rigidity, bradykinesia, ptosis, PEO, Muscle weakness, cataracts, Neuropathy. | | | 49 | 73 | n/a | Luoma et al, 2004; [view data] | | 667 | | Y955C1
| Parkinsonism, restless legs syndrome. Good response to levodopa and ropinirole. PEO, cerebellar ataxia, neuropathy, myopathy, sensorineural hearing loss. | | - | movement disorder (ataxia) | |
| | 40 | 63 | n/a | Martikainen et al, 2016; [view data] | | 527 | | D890A1
| The patient had bilateral cataracts removed in early childhood. He developed chronic diarrhea and weight loss in his 20s, which were associated with a rash that on biopsy showed features of dermatitis herpetiformis. At the age of 35 years, the patient presented with weakness of upper extremities and bilateral ptosis. A muscle biopsy revealed ragged-red fibers and cytochrome c oxidase (COX) negative fibers. impaired upgaze. cachexia. chronic myopathy and severe sensory neuropathy. progressive gastrointestinal dysmotility. mtDNA deletions. hypogonadism, hypothyroidism, and osteopenia. | | | 22 | 35 | n/a | Prasun and Koeberl, 2014; [view data] | | 560 | | Y955C1
| Ptosis, Ophthalmoplegia, Dysphonia, Dysphagia, Muscle weakness, Loss of weight, Elevated blood CK, Myogenic EMG, Distal sensory neuropathy, areflexia, Psychatric symptoms. | | | 25 | 60 | n/a | Van Goethem et al, 2001; [view data] | | 561 | | Y955C1
| Ptosis, Ophthalmoplegia, Dysphonia, Dysphagia, Muscle weakness, Elevated blood CK, Myogenic EMG, ocular symptoms, areflexia. | | | 35 | 55 | n/a | Van Goethem et al, 2001; [view data] | | 562 | | Y955C1
| Psychiatric symptoms, ptosis, Ophthalmoplegia, Dysphonia, Dysphagia, Muscle weakness, Elevated blood CK, Myogenic EMG, areflexia, distal sensory neuropathy, hearing loss. | | | 30 | 48 | n/a | Van Goethem et al, 2001; [view data] | | 563 | | Y955C1
| Ocular symptoms, ptosis, Ophthalmoplegia, Muscle weakness, areflexia. | | | 35 | 53 | n/a | Van Goethem et al, 2001; [view data] | | 564 | | Y955C1
| Ocular symptoms, ptosis, Ophthalmoplegia, Muscle weakness, areflexia. | | | 30 | 52 | n/a | Van Goethem et al, 2001; [view data] | | 565 | | Y955C1
| Ocular symptoms, ptosis, Ophthalmoplegia, Muscle weakness, areflexia. | | | 39 | 39 | n/a | Van Goethem et al, 2001; [view data] | | 566 | | Y955C1
| Ocular symptoms, ptosis, areflexia. | | | 33 | 33 | n/a | Van Goethem et al, 2001; [view data] | | 567 | | Y955C1
| Ocular symptoms, ptosis, dysphonia, distal sensoral neuropathy, areflexia, pes cavus. | | | 32 | 32 | n/a | Van Goethem et al, 2001; [view data] | | 568 | | Y955C1
| Neuropathic symptoms, psychiatric symptoms, distal sensoral neuropathy, areflexia, pes cavus. | | | 28 | 29 | n/a | Van Goethem et al, 2001; [view data] | | 606 | | Y955C1
| PEO. | | | n/a | 31 | n/a | Lamantea et al, 2002; [view data] | | 607 | | Y955C1
| PEO. | | | n/a | 54 | n/a | Lamantea et al, 2002; [view data] | | 608 | | R943H1
| adPEO. | | | n/a | 50 | n/a | Lamantea et al, 2002; [view data] | | 621 | | S1104C1
| PEO, bilateral ptosis, severe limitation 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. | | | 42 | n/a | n/a | Agostino et al, 2003; [view data] | | 381 | | Y955C1
| Presented with ptosis and PEO, in early 20’s, premature ovarian failure at 32 years, proximal muscle weakness, exertional dyspnoea and sensory ataxia, dysphagia. | | - | movement disorder (ataxia) | |
| | 22 | n/a | n/a | Pagnamenta et al, 2006; [view data] | | 204 | | R943H1
| Age 71 with CPEO and premature ovarian failure. | | | n/a | 71 | n/a | Blok et al, 2009; [view data] | | 206 | | Y951N1
| Peripheral neuropathy, elevated 3-methylglutaconic acid. | | | n/a | 22 | n/a | Tang et al, 2011; [view data] | | 209 | | Y955C1
| CPEO, myopathy. | | | n/a | 45 | n/a | Tang et al, 2011; [view data] | | 210 | | Y955C1
| CPEO, myopathy. Muscle biopsy showed RRF, multiple mtDNA deletions. Age of onset for three alcoholics ranged from 25-39, and age of death ranged from 54-65. | | | 25 | n/a | 54 | Van Goethem et al, 2003a; [view data] | | 238 | | A889T1
E1143G
| Presented with ataxia and transient diplopia at age 25 and showed ptosis, external ophthalmoplegia, nystagmus, had a mild tremor of outstretched hands, marked dysmetria, Romberg sign, severe ataxia, was unable to stand on one foot, multiple mtDNA deletions in muscle. | | - | movement disorder (ataxia) | |
| - | external ophthalmoplegia | |
| | n/a | 25 | n/a | Hisama et al, 2005; [view data] | | 239 | | Y955C1
| adPEO, multiple mtDNA deletions in muscle tissue. | | | 55 | 55 | n/a | Kollberg et al, 2005; [view data] | | 247 | | Y955C1
| adPEO, multiple mtDNA deletions in muscle tissue. | | | n/a | 53 | n/a | Kollberg et al, 2005; [view data] | | 248 | | Y955C1
| adPEO, multiple mtDNA deletions in muscle tissue. | | | n/a | 60 | n/a | Kollberg et al, 2005; [view data] | | 249 | | Y955C1
| adPEO, multiple mtDNA deletions in muscle tissue. | | | n/a | 60 | n/a | Kollberg et al, 2005; [view data] | | 291 | T914A1
| Y452C
| presented with blurred vision, elevated CSF protein, she successively developed various neurological signs, ie, bilateral external ophthalmoplegia, ataxia, hearing impairment, and severe depression, ptosis, myopathy, cardiomyopathy, and dysphagia, multiple mtDNA deletions in muscle | | - | movement disorder (ataxia) | |
| - | external ophthalmoplegia | |
| | 37 | 56 | n/a | Echaniz-Laguna et al, 2010; [view data] | | 350 | T851A1
| P163S
| CPEO, Seizures, neuropathy, ataxia, dysphagia/ dysarthria, bowel pseudo-obstruction, | | - | movement disorder (ataxia) | |
| | 21 | n/a | n/a | Woodbridge et al, 2012; [view data] | | 379 | Q1236H
| Y955C1
| Presented with ptosis and PEO, in early 20’s, premature ovarian failure at 28 years. proximal muscle weakness, exertional dyspnoea and sensory ataxia, Peripheral neuropathy | | - | movement disorder (ataxia) | |
| | 22 | 33 | n/a | Pagnamenta et al, 2006; [view data] | | 380 | | Y955C1
| Presented with ptosis and PEO, in early 20’s, premature ovarian failure at 35 years, proximal muscle weakness, exertional dyspnoea and sensory ataxia, dysphagia. At the age of 57, patient III-2 was noted to have a progressive, parkinsonian-like resting tremor and reduced rapid alternating movements affecting her left arm and leg, and mild bradykinesia. ragged-red fibres | | - | movement disorder (ataxia) | |
| | 22 | 57 | n/a | Pagnamenta et al, 2006; [view data] | | 494 | | Y955C1
| Parkinsons, resting tremor, rigidity, bradykinesia, ptosis, PEO, Muscle weakness, Neuropathy | | | 49 | 50 | n/a | Luoma et al, 2004; [view data] | | 436 | | D1184N1
| CPEO, axonal sensory neuronopathy, parkinsonism. late-onset CPEO with a sensory neuropathy and a Parkinsonian syndrome. | | - | axonal sensorimotor polyneuropathy | |
| | 70 | n/a | n/a | Rouzier et al, 2013; [view data] | | 437 | | D1184N1
| CPEO, axonal sensory neuronopathy. | | - | axonal sensorimotor polyneuropathy | |
| | 75 | n/a | n/a | Rouzier et al, 2013; [view data] | | 438 | G848S1
| T251I
| CPEO, multiple mtDNa deletions. | | | 45 | n/a | n/a | Rouzier et al, 2013; [view data] | | 444 | | R943H1
| At age 63: CPEO, ptosis, congenital cataracts, vision loss with macular degeneration, hearing loss, dysarthria, dysphagia, sensorimotor polyneuropathy, fatigue, migraine, cardiomyopathy and depression. At age 67, he developed asymmetric resting tremor and impaired balance. Examination at age 71 revealed CPEO, facial diplegia, mild symmetric rigidity, intermittent, pre- dominantly right-sided resting tremor and multidirectional head tremor, bradykinesia, and ataxic gait (broad based stance with inability to tandem). Brain MRI showed mild atrophy and very subtle multifocal subcortical white matter lesions. | | - | movement disorder (ataxia) | |
| - | axonal sensorimotor polyneuropathy | |
| | 63 | 71 | n/a | Brandon et al, 2013; [view data] | | 474 | | F961S1
| Mother of Japanese adPEO family. The proband, 69 years female, developed bilateral blepharoptosis and external ophthalmoplegia at forty. She also had slight muscle weakness and atrophy of proximal limbs and neck. Her mother, one of her three siblings and her daughter had same symptoms. Muscle biopsy examination of her and her brother showed several ragged red fibers. | | - | external ophthalmoplegia | |
| | 40 | 69 | n/a | Adachi et al, 2002; [view data] | | 481 | | H945L1
| 80-year old female patient with a history of PEO, ptosis, childish behaviour, obsessive disorder, cognitive decline, and parkinsonism. Progressive bilateral ptosis in her forties. She also suffered progressive cognitive decline, with difficulties in performing her habitual tasks and a degree of social impairment. In addition, a loss of facial expression had become evident in the last few years. Physical examination showed bilateral ptosis with right predominance, PEO, dysphonia, right hand rest tremor, bilateral mild rigidity and bradykinesia in the upper extremities. A brain MRI scan revealed moderate enlargement of the ventricles and diffuse brain atrophy. muscle biopsy of the biceps brachii demonstrated ragged red fibres based on Gomori staining. Southern blot hybridization analysis identified multiple mtDNA deletions that were confirmed using the long-PCR technique. | | | 30 | 80 | n/a | Delgado-Alvarado et al, 2015; [view data] | | 486 | | Y955C1
| ptosis, weak achilles tendon reflexes | | | 33 | 38 | n/a | Luoma et al, 2004; [view data] | | 487 | | Y955C1
| Parkinsons, rigidity, bradykinesia, ptosis, PEO, muscle weakness, hypoacusia, premature menopause. | | | 30 | 67 | n/a | Luoma et al, 2004; [view data] | | 488 | | Y955C1
| Parkinsons, resting tremor, rigidity, bradykinesia, ptosis, PEO, muscle weakness, Cataracts, presbyacusis, ataxia, premature menopause, neuropathy. | | - | movement disorder (ataxia) | |
| | 22 | 60 | 61 | Luoma et al, 2004; [view data] | | 489 | | Y955C1
| PEO, Parkinsons, rigidity, bradykinesia, ptosis, muscle weakness, cataracts, ataxia. | | - | movement disorder (ataxia) | |
| | 35 | 60 | n/a | Luoma et al, 2004; [view data] | | 490 | | Y955C1
| PEO, Parkinsons, rigidity, resting tremor, bradykinesia, ptosis, muscle weakness, cataracts, ataxia. | | - | movement disorder (ataxia) | |
| | 25 | 58 | 60 | Luoma et al, 2004; [view data] | | 491 | | Y955C1
| PEO, Primary amenorrhea, Parkinsons, resting tremor, rigidity, bradykinesia, ptosis, muscle weakness, mental retardation, cataracts, ataxia, head tremor | | - | movement disorder (ataxia) | |
| | 23 | 64 | n/a | Luoma et al, 2004; [view data] | | 492 | | Y955C1
| PEO, premature menopause, Parkinsons, resting tremor, rigidity, bradykinesia, ptosis, cataracts, ataxia. | | - | movement disorder (ataxia) | |
| | 21 | 62 | n/a | Luoma et al, 2004; [view data] | | 493 | | Y955C1
| PEO, ptosis, muscle weakness | | | 23 | 33 | n/a | Luoma et al, 2004; [view data] | | 595 | E1143G
| S433C1
| PEO, ataxia, peripheral neuropathy, and episodes of encephalopathy. Asymptomatic mother had also S433C. | | - | movement disorder (ataxia) | |
| | n/a | n/a | n/a | Hudson et al, 2006; [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: 68
Avg age of onset in displayed cases: 33.1
Std dev in onset in displayed cases: 18.6
|