From: Genetic insights into PHARC syndrome: identification of a novel frameshift mutation in ABHD12
Nucleotide change* | AA change | E I | Mutation type | Age Sex | Poly neuropathy | Motor Neuropathy | HL | RP | ERG | Cataract | Ataxia | MR CT | Pyramidal Tract Signs | Other | Country | Family case | Ref |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
14Â kb deletion removing exon 1 | Â | E1 | Deletion | 24Â M | Abnormal | Pes cavus; absent tendon reflexes | 14y Deaf | 20y | NR | 15y | Mild | Normal | Indifferent plantar response | No | UAE | 6.1 | [7] |
14Â kb deletion removing exon 1 | Â | E1 | Deletion | 20Â M | Demyelinating polyneuropathy | Pes cavus; absent tendon reflexes | 6y | Yes | NR | Yes | Speech and limb ataxia; wheelchair-bound (10y) | Cerebellar atrophy 3y | Extensor plantar response | No | UAE | 6.2 | [7] |
14Â kb deletion removing exon 1 | Â | E1 | Deletion | 6Â F | NR | Absent tendon reflexes | Yes | No | NR | Yes | Speech and limb | Cerebellar atrophy | Indifferent plantar response | No | UAE | 6.3 | [7] |
c.193 C > T | p.Arg65* | E2 | Nonsense | 55 F | No | No | 17y 35y CI | Yes | Rod-cone abnormal | Yes | Ataxic gait with poor tandem walking; action tremor with writing cramp and involuntary athetotic movements of her fingers | Normal | NR | Night blindness, glaucoma | Lebanese | II.1 | [41] |
c.193 C > T | p.Arg65* | E2 | Nonsense | 53 M | NR | NR | 24y 35y CI | Yes | NR | Posterior subcapsular cataract | NR | NR | NR | Glaucoma; severe optic atrophy | Lebanese | II.4 | [41] |
c.193 C > T | p.Arg65* | E2 | Nonsense | 22 M | Yes | 7y; Lack of coordination | No | Yes | Rod-cone dystrophy | No | NR | NR | NR | No | NR | ABHD12-3  H-10 | |
c.211-223del | p.Arg71Tyrfs*26 | E2 | Frameshift | 42Â M | Demyelinating polyneuropathy | Pes cavus; hammertoes; sensory loss; | 43y bilaterally CI | Yes | Rod-cone dystrophy | 38y | Wide-base gait, action tremor in the upper limbs | Mild cerebellar atrophy | NR | muscle MRI revealed mild fatty infiltration in the intrinsic muscles of both feet and the anterior compartment of the left leg | Spanish | II.3 | [37] |
c.211-223del | p.Arg71Tyrfs*26 | E2 | Frameshift | NR M | Demyelinating polyneuropathy | Pes cavus; hammertoes; sensory loss | 18y | Yes | NR | Yes | Wide-base gait; dysarthria; slight dysmetria | Mild cerebellar atrophy | NR | No | Spanish | II.1 | [37] |
c.249 C > G | p.Tyr83* | E2 | Nonsense | 41 M | NR | NR | 32y progressive | Yes | Abnormal | Yes | NR | NR | NR | Olfactory decline | China | I.1 | [36] |
c.249 C > G | p.Tyr83* | E2 | Nonsense | 31 M | NR | NR | 32y progressive | Yes | NR | Yes | NR | NR | NR | Olfactory decline | China | II.5 | [36] |
c.259 C > A c.1063 C > T | p. Pro87Thr p.Arg355* | E2 E12 | Missense Nonsense | 28 F | NR | NR | No | Yes | Rod-cone dystrophy | No | No | NR | NR | No | NR | ABHD12-2 | [34] |
c.316 + 2T > A |  | I2 | Splice site | 56 M | Yes | Sensory loss | 15y 41y CI | 22y | NR | Yes | Steppage gait | Normal | NR | No | Japan | KTM 5012 | [39] |
c.316 + 2T > A |  | I2 | Splice site | 64 M | NR | NR | Progressive | 45y | NR | Yes | NR | Cerebral and cerebellar atrophy | NR | Epilepsy; 30y night blindness | Japan | SNS5547 | [39] |
c.316 + 2T > A |  | I2 | Splice site | NR M | NR | NR | Deaf | Yes | NR | Yes | NR | NR | NR | Epilepsy | Japan | SNS5548 | [39] |
c.319delA c.605 C > T | p.Arg107Glufs*8 p.Thr202Ile | E3 E6 | Frameshift Missense | 78 F | No | Decreased vibration sense in lower limbs | Presbycusis | Yes | NR | Yes | No | Minimal cerebral atrophy | No | No | Spain | 1292-II.4 | [40] |
c.319delA c.605 C > T | p.Arg107Glufs*8 p.Thr202Ile | E3 E6 | Frameshift Missense | 75 M | No | Slightly loss of strength right upper limb | Presbycusis | Yes | NR | Yes | Dysmetria in lower limbs; slightly wide basegait | Normal | No | No | Spain | 1292-II.5 | [40] |
c.319delA c.605 C > T | p.Arg107Glufs*8 p.Thr202Ile | E3 E6 | Frameshift Missense | 72 F | No | No | NR | Yes | NR | Yes | Gait somewhat unstable | NR | No | No | Spain | 1292-II.6 | [40] |
c.319delA c.605 C > T | p.Arg107Glufs*8 p.Thr202Ile | E3 E6 | Frameshift Missense | 66 M | No | No | Presbycusis | Yes | Diminished | Yes | Slight dysarthria; mild distal postural tremor | Normal | No | No | Spain | 1292-II.7 | [40] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 62Â F | Demyelinating polyneuropathy | 38y; pes cavus; sensory loss; absent ankle reflexes | 20y | 38y | Rod-cone dystrophy | 28y | No | Normal | No | No | Norway | 1.1 | [7] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 56Â M | Demyelinating polyneuropathy | 37y; pes cavus | 30y | 37y | Rod-cone dystrophy | 37y | 37y; gait ataxia | Normal | Extensor plantar response at lower limbs; spasticity; hyperreflexia | No | Norway | 1.2 | [7] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 46Â M | Demyelinating polyneuropathy | 38y; distal sensory loss | Yes | 46y | Rod-cone dystrophy | 25y | 43y; gait ataxia; upper limb intention tremor | Cerebellar atrophy | Extensor plantar response at lower limbs; spasticity; hyperreflexia | No | Norway | 1.3 | [7] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 58Â M | Demyelinating/ axonal polyneuropathy | 51y; pes cavus; sensory loss; reduced tendon reflexes | 20y | 35y | Rod-cone dystrophy | 26y | No | Cerebellar atrophy | Extensor plantar response at lower limbs | No | Norway | 2.1 | [7] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 54Â F | Yes | 53y; pes cavus; reduced tendon reflexes | 20y | 25y | Flat | 25y | No | NR | No | NO | Norway | 2.2 | [7] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 36Â F | Demyelinating polyneuropathy | Pes cavus; reduced tendon reflexes in lower limbs | 10y Deaf | 36y | Rod-cone dystrophy | 32y | Yes | Atrophy of vermis and medulla oblongata | Extensor plantar response at right side; spasticity | No | Norway | 3.1 | [7] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 24Â M | Demyelinating polyneuropathy | Pes cavus; hammertoes; reduced tendon reflexes in upper and lower limbs | Yes | No | Normal | 15y | No | Slight ventricular asymmetry | Indifferent plantar response | No | Norway | 4.1 | [7] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 16Â M | Demyelinating polyneuropathy | Pes cavus; reduced sensibility; reduced tendon reflexes in upper limbs, absent in lower limbs | 13y | No | Normal | 16y slight | No | Normal | No | No | Norway | 5.1 | [7] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 20Â M | Yes | NR | 16y | Yes | NR | Star-shaped cataract 17y | No | Cerebellar atrophy | NR | No | NR | J-12 | [8] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 17Â M | Yes | NR | 10y | Yes | NR | Star-shaped cataract 10y | No | Cerebellar atrophy | NR | No | NR | J-13 | [8] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 36Â F | NR | NR | 12y | Yes | Rod-cone dystrophy | Posterior subcapsular cataract 32y | Yes | NR | NR | No | NR | E-7 | [8] |
c.337-338delGAinsTTT | p.Asp113Phefs*15 | E3 | Frameshift | 32Â F | Yes | NR | 17y | Yes | Rod-cone dystrophy | Posterior subcapsular cataract 32y | 45y | NR | NR | No | NR | B-2 | [8] |
c.337-338delGAinsTTT c.341dup | p.Asp113Phefs*15 p.Leu114Phefs*14 | E3 E3 | Frameshift Frameshift | 39Â M | NR | NR | 33y | Yes | Rod-cone dystrophy | Star-shaped cataract 29y | NR | NR | NR | No | NR | L-15 | [8] |
c.337-338delGAinsTTT c.423-1_425del | p.Asp113Phefs*15 p.(?) | E3 I3 | Frameshift Splice site | 33Â M | Yes | Subtle foot drop; absent Achilles tendon reflexes | No | Yes | NR | Sutural cataract 3y | 27y | Normal | NR | No | NR | C-3 | [8] |
c.337-338delGAinsTTT c.423-1_425del | p.Asp113Phefs*15 p.(?) | E3 I3 | Frameshift Splice site | 33Â M | Yes | Distal muscle weakness; sensory loss | Yes | Yes | Â | Sutural cataract 3y | 27y | Normal | NR | No | NR | C-4 | [8] |
c.337-338delGAinsTTT c.423-1_425del | p.Asp113Phefs*15 p.(?) | E3 I3 | Frameshift Splice site | 38Â M | Yes | Abnormal gait pattern; distal sensory loss | 20y | Yes | Â | Star-shaped cataract 4y | 31y | Cerebellar atrophy | NR | No | NR | C-5 | [8] |
c.337-338delGAinsTTT c.1075del | p.Asp113Phefs*15 p.Val359Phefs*27 | E3 E12 | Frameshift Frameshift | 47Â M | Yes | Pes cavus, hammertoes, distal sensory loss, absent tendon reflexes 8y | 28y | Yes | Rod-cone dystrophy | 36y | 8y | Normal | NR | No | NR | A-1 | [8] |
c.374 C > T c.1154T > C | p.Thr125Met p.Leu385Pro | E3 E12 | Missense Missense | 53 M | NR | NR | 44y progressive | Yes | NR | Posterior polar cataract 41y | NR | NR | NR | Epilepsy; learning difficulties | NR | ABHD12-5 I-11 | (8, 34) |
c.379-385del AACTACT ins GATTCCTTATAT ACCATTGTAGTC TTACTGCTTTTG GTGAACACA | p.Asn127Aspfs*23 | E3 | Deletion-Insertion | 36Â M | Demyelinating polyneuropathy | Yes | 5y Deaf | No | NR | 28y | 15y ataxic walk | Normal | NR | No | France | XIX.1 | [12] |
c.447G > A c.557G > C | p.Trp159* p.Arg186Pro | E4 E5 | Nonsense Missense | 30 M | Yes | Distal sensory loss; reduced tendon reflexes | Yes | Yes | Rod-cone dystrophy | Cortical cataract | Wide-based gait; Stuttering speech; ataxic gait | Normal | No | No | Netherlands | W08-1833 D-6 | (8, 40) |
c.601dup | p.Val201Glyfs*4 | E6 | Frameshift | 25Â M | Yes | Pes cavus; slight gait disturbance | Yes | Yes | Abnormal | Yes | Yes | Cerebellar atrophy | No | No | Iran | IV.1 | This study |
c.601dup | p.Val201Glyfs*4 | E6 | Frameshift | 18Â F | Yes | Pes cavus | Yes | Yes | Abnormal | Yes | No | Normal | No | No | Iran | IV.2 | This study |
c.620–2 A > G |  | I6 | Splice site | 34 M | Yes | 31y; Lower limb muscle weakness | 20y progressive | Yes | Rod-cone dystrophy | 26y | No | NR | NR | No | NR | ABHD12-4 G-9 | (8, 34) |
c.758 C > G | p.Thr253Arg | E8 | Missense | 31 F | Demyelinating polyneuropathy | Sensory loss | 31y bilateral CI | Yes | NR | Posterior subcapsular cataract8y | ataxia 16y; mild intentional tremor; mild dysarthria; wheelchair-bound | Normal | NR | Decreased function of the labyrinths | Swedish | II.1 | [38] |
c.784 C > T c.867 + 5G > A | p.Arg262* | E8 I9 | Nonsense Splice site | 53 M | Yes | 53y; Distal sensory loss | 20y progressive | Yes | NR | No | No | NR | NR | No | NR | ABHD12-6  F-8 | (8, 34) |
c.784 C > T | p.Arg262* | E8 | Nonsense | 21 M | Demyelinating polyneuropathy | Pes cavus: reduced tendon reflexes at upper and lower limbs | 9y 17y CI | No | NR | Yes | Stance ataxia | Cerebellar atrophy | No | No | Iraq | A | [35] |
c.784 C > T | p.Arg262* | E8 | Nonsense | 25 M | Demyelinating polyneuropathy | Sensory loss; Loss of Achilles and patellar tendon reflexes | 12y 18y CI | Yes | NR | Yes | Slight bilateral limb ataxia | NR | NR | No | Iraq | B | [35] |
c.846-852dupTAAGAGC | p.His285fs*1 | E9 | Frameshift | 11Â M | Yes | Absent tendon reflexes; moderate muscle weakness at lower limbs | No | No | NR | No | 3-4y; limb ataxia ; horizontal nystagmus; dysarthria; dysmetria delayed walking at 15 months; action and intention tremor | Cerebellar atrophy | Extensor planter response at lower limbs | No | Algeria | 8.1 | [7] |
c.846-852dupTAAGAGC | p.His285fs*1 | E9 | Frameshift | 10Â F | Yes | Absent tendon reflexes at lower limbs | No | No | NR | No | 4-5y; gait ataxia | Vermian atrophy | Extensor planter response at lower limbs | No | Algeria | 8.2 | [7] |
c.846-852dupTAAGAGC | p.His285fs*1 | E9 | Frameshift | 44Â M | Demyelinating polyneuropathy | Pes cavus; sensory loss; absent tendon reflexes at lower limbs; scoliosis | Yes | Amblyopia | NR | NR | 7-10y limb ataxia; dysarthria; dysmetria at upper limbs with adiadocokinesia; head titubation | Vermian atrophy | Extensor planter response at lower limbs; macroglossia | No | Algeria | 9.1 | [7] |
c.846-852dupTAAGAGC | p.His285fs*1 | E9 | Frameshift | 26Â F | Demyelinating polyneuropathy | Pes cavus; sensory loss; reduced tendon reflexes at upper limbs, and absent at lower limbs; tongue fasciculation | Deaf | Yes | NR | Yes | 4-9y gait and limb ataxia; horizontal nystagmus; moderate dysarthria; dysmetria at upper and lower limbs | Vermian atrophy | Extensor planter response at lower limbs; | No | Algeria | 9.2 | [7] |
c.846-852dupTAAGAGC | p.His285fs*1 | E9 | Frameshift | 26Â F | Severe demyelinating polyneuropathy on nerve biopsy | Pes cavus; sensory loss; absent tendon reflexes | 6y | No | NR | No | 6-12y limb ataxia | Normal | Indifferent plantar response | No | Algeria | 10.1 | [7] |
c.846-852dupTAAGAGC | p.His285fs*1 | E9 | Frameshift | 19Â F | Yes | 12y; pes cavus; sensory loss; absent tendon reflexes at upper and lower limbs | NR | NR | NR | NR | No | NR | NR | No | Algeria | 10.2 | [7] |
c.846-852dupTAAGAGC | p.His285fs*1 | E9 | Frameshift | 32Â F | Axonal polyneuropathy | Pes cavus; sensory loss; absent tendon reflexes at lower limbs | Yes | Decreased visual acuity and amblyopia | NR | No | 16-20y; gait ataxia; dysarthria; dysmetria at upper limbs | Cerebellar atrophy | Extensor plantar response at lower limbs | No | Algeria | 11.1 | [7] |
c.846-852dupTAAGAGC | p.His285fs*1 | E9 | Frameshift | 23Â F | Yes | NR | Yes | Yes | NR | Yes | Yes | NR | NR | No | Spain | 10 | [42] |
c.1054 C > T | p.Arg352* | E12 | Nonsense | 50 F | Abnormal | 34y; pes cavus; hammertoes; | 17y | 20y | NR | 22y | 18y; dysarthria; gait ataxia; jerky eye movement tremor in hand | Cerebellar atrophy Increased signal in periventricular white matter | Flexor planter response; spasticity; | No | USA | 7.1 | [7] |
c.1054 C > T | p.Arg352* | E12 | Nonsense | 29 F | Demyelinating polyneuropathy | Pes cavus; sensory loss; absent tendon reflexes; a mild waddling | 16y | Yes | NR | Yes | Gait ataxia; progressive jerky tremor; mild titubation of the trunk; mild proximal tetraparesis; dysmetria; mild bilateral ptosis; congenital convergent strabismus | Global moderate cerebral/cerebellar atrophy | NR | Mild learning disabilities | Portugal |  | [9] |
c.1054 C > T c.1196del | p.Arg352* p.*399Serfs*122 | E12 E13 | Nonsense | 48 F | NR | NR | No | yes | No Rod-cone dystrophy | Yes | No | NR | NR | No | NR | ABHD12-1 | [34] |
c.1063 C > T | p.Arg355* | E12 | Nonsense | 46 F | Yes | NR | Yes | Yes | Rod-cone dystrophy | Cerulean cataract | Yes | NR | NR |  | NR | K-14 | [8] |
c.1116 C > G | p.His372Gln | E12 | Missense | 38 F | Demyelinating polyneuropathy | Distal symmetric hypoesthesia to touch and pain; achilles reflex abolished | 38y | Yes | Diminished | Yes | No | Cerebral and cerebellar atrophy | NR | No | Spain | RP-1487 | [40] |
c.1129 A > T 59 Kb deletion including exon 1 | p.Lys377* | E12 E1 | Nonsense Deletion | 29 F | Demyelinating polyneuropathy | Pes cavus; sensory loss; absent tendon reflexes | HL from Childhood 21y bilateral CI | Yes | Abnormal | Yes | Steppage gait; mild dysmetria | Normal | Flexor plantar response | No | Japan | III.1 | [11] |