Table 2 Summary of the clinical, neuroimaging, and genetic features of Gordon Holmes patients with PNPLA6, STUB1 and OTUD4 genes mutations (Adopted from Gonzales- Latapi et al. [2] and Wu et al. [11]
From: A novel mutation in RNF216 gene in a Turkish case with Gordon Holmes syndrome
Family and Patient (Author) | Sex | Age of onset (years) | Clinical type | Clinical feature | Pubertal development | Imaging findings | Genotype and mutation |
|---|---|---|---|---|---|---|---|
F1-P1 (Margolin, DH. et al.) | M | 22 | GHS | Ataxia, dementia | No puberty | Cerebellar and cerebral atrophy, cerebral WMLs | OTUD4 pG333V and RNF216 p.R751C |
F1-P2 (Margolin, DH. et al.) | F | 16 | GHS | Personality change, ataxia, dementia, | Secondary amenorrhea | Cerebellar and cortical atrophy, hrpoerintensitieas in cerebral white matter | OTUD4 pG333V and RNF216 p.R751C |
F1-P3 (Margolin, DH. et al.) | M | 29 | GHS | Ataxia, dementia, | Normal puberty Erectile dysfunction | Cerebral and diffuse cortical atrophy, multiple punctate and confluent areas of hyperintensity | OTUD4 pG333V and RNF216 p.R751C |
F2-P2 (Shi, C. et al.) | F | 17 | GHS | Gait ataxia Appendicular ataxia Cerebellar ocular abnormalities Hand tremor and coarse head tremor Pyramidal signs Cognitive impairment | Hypogonadotropic Primary amenorrhea Underdeveloped secondary sexual characters Hypoplasia of uterus and ovaries | Cerebellar atrophy | STUB1 homozygous mutation (c. 737C > T) |
F2-P3 (Shi, C. et al.) | F | 19 | GHS | Gait ataxia Appendicular ataxia Cerebellar ocular abnormalities Cognitive impairment | Hypogonadotropic Primary amenorrhea Underdeveloped secondary sexual characters Hypoplasia of uterus and ovaries | Cerebellar atrophy | STUB1 homozygous mutation (c. 737C > T) |
F3-P4 Hayer SN, et al., | M | 12 | GHS | Ataxia, spasticity, bilateral Babinski’s sign, focal dystonia, hypomimia, severe cognitibe impairment, urge incontinence Epilepsy | hypogonadism | Cerebellar, mesencephalic and parieto-occipital cortical atrophy | STUB! c.880A > T (p.Arg119*) c.880A > T (p.Ile294Phe) |
F3-P5 Hayer SN, et al., | M | 12 | GHS | Ataxia, spasticity, urge incontinence, intermittent ballistic athetotic movements, epilepsy, severe cognitive impairment, mutism | normal | Cerebellar atrophy | STUB! c.433A > C (p.Lys145Gln) |
F3-P6 Hayer SN, et al., | F | 20 | GHS | Spasticity, intermittent ballistic athetotic movements, epilepsy,severe cognitive impatiment, mutism | n/a | Severe cerebellar atrophy, vermis and hemispheric atrophy | STUB! c.433A > C (p.Lys145Gln) |
F4-P7 (Synofzik, M. et al.) | M | 6 | GHS | Dysarthria, ataxia, brisk tendon reflexes | Delayed puberty | Cerebellar atrophy, empty sella | PNPLA6 c.3084_3085insGCCA p.Arg1031Glufs*38 c.4084C 4G p.Arg1362Gly |
F 5-P8 (Teive, H. et al.) | M | 23 | GHS | Ataxia | Poor development of puberty | Mild cerebellar atrophy | PNPLA6 c.4081C > T, p.Arg1381* c.3373G > A, p.Asp1125Asn |
F6- P9 (Locci, S. et al.) | M | 25 | Spastic ve ataxic gait, central nystagmus in the lateral gaze, slight dysmetria, dysdiadochokinesia, milf pyramidal hypertonia, bilateral ankle clonus, brisk deep tendon reflexes | Poor development of puberty | Cerebellat atrophy, small bilateral hyperintense lesions in the periventricular white matter | PNPLA6 c.2264 A > C; (p.Gln755Pro) c 0.3388 C > T; (p.His1130Tryr) | |
F7- P10 (Salgado, P. et al.) | F | 25 | GHS | Gait ataxia, mild dysarthria, cognitive decline, horizontal and vertical gaze-evoked nystagmus, postural hand tremor | No puberty | Cerebellar and vermis atrophy | PNPLA6 compound heterozygosity [c.2404G > C]; p.(Glu802Gln); [c.4081C > T],p.(Arg1361*) |
F7- P11 (Salgado, P. et al.) | F | N/R | GHS | Cognitive decline | No puberty | Cerebellar atrophy | PNPLA6 compound heterozygosity [c.2404G > C]; p.(Glu802Gln); [c.4081C > T],p.(Arg1361*) |
F7- P12 (Salgado, P. et al.) | F | N/R | GHS | Ataxia and tremor, cognitive decline | No puberty | Cerebellar atrophy | PNPLA6 compound heterozygosity [c.2404G > C]; p.(Glu802Gln); [c.4081C > T],p.(Arg1361*) |
F7- P13 (Salgado, P. et al.) | F | N/R | GHS | Ataxia and tremor, epilepsy and migraine, cognitive decline | No puberty | Cerebellar atrophy | PNPLA6 compound heterozygosity [c.2404G > C]; p.(Glu802Gln); [c.4081C > T],p.(Arg1361*) |
F8-P14 Topaloğlu, H., et al | M | 37 | Gait ataxia, dysartria | Poor development of puberty | Cerebellar atrrophy | PNPLA6 c.3380C > G; p.S1127C | |
F8- P15 Topaloğlu, H., et al | F | 20 s | Gait ataxia | Hypogonadotrophic hypogonadism | Cerebellar atrrophy | PNPLA6 c.3380C > G; p.S1127C | |
F8-P16 Topaloğlu, H., et al | M | N/R | 21 | Gait ataxia | Hypogonadotrophic hypogonadism | Cerebellar atrrophy | PNPLA6 c.3380C > G; p.S1127C |
F8-P17 Topaloğlu, H., et al | M | 18 | Nystagmus, gait ataxia, dysartira | N puberty | Cerebellar atrophy | PNPLA6 c.3380C > G; p.S1127C | |
F8-P18 Topaloğlu, H., et al | M | 15 | N/R | No puberty | N | PNPLA6 c.3380C > G; p.S1127C |