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| Cerebral Palsy v1.291 | PIDD1 |
Clare van Eyk gene: PIDD1 was added gene: PIDD1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIDD1 were set to PMID: 38693247 Phenotypes for gene: PIDD1 were set to Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM#619827 Review for gene: PIDD1 was set to RED Added comment: 1 individual reported with biallelic LOF variants reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. PIDD1 is associated with an intellectual developmental disorder with variant lissencephaly. Sources: Literature |
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| Cerebral Palsy v1.200 | ATR | Zornitza Stark Marked gene: ATR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.200 | ATR | Zornitza Stark Gene: atr has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.200 | ATR | Zornitza Stark Classified gene: ATR as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.200 | ATR | Zornitza Stark Gene: atr has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.194 | ATR |
Clare van Eyk gene: ATR was added gene: ATR was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ATR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATR were set to PMID: 38693247 Phenotypes for gene: ATR were set to Seckel syndrome, MIM#210600 Review for gene: ATR was set to RED Added comment: 1 individual reported with biallelic splice variants in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Sources: Literature |
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| Cerebral Palsy v1.194 | NR2F1 |
Clare van Eyk gene: NR2F1 was added gene: NR2F1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: NR2F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NR2F1 were set to PMID: 38693247 Phenotypes for gene: NR2F1 were set to Bosch-Boonstra-Schaaf optic atrophy syndrome, MIM#615722; NR2F1-related neurodevelopmental disorder Review for gene: NR2F1 was set to RED Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided. Sources: Literature |
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| Cerebral Palsy v1.190 | ATRX | Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.189 | ATRX | Zornitza Stark edited their review of gene: ATRX: Changed phenotypes: ATR-X-related syndrome MONDO:0016980 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.144 | SEPSECS |
Luisa Weiss gene: SEPSECS was added gene: SEPSECS was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SEPSECS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEPSECS were set to 33528536; 35252561; 34540776; 36085396 Phenotypes for gene: SEPSECS were set to Pontocerebellar hypoplasia type 2D MIM#613811 Review for gene: SEPSECS was set to GREEN Added comment: Biallelic SEPSECS mutations have been described to cause Pontocerebellar hypoplasia type 2D, which usually presents with progressive microcephaly, progressive brain atrophy, ID and variable seizures and movement disorders. There have been two cases in two large CP cohort studies (33528536, 34540776) which have been proven to harbor biallelic SEPSECS variants, however, in PMID 34540776 these can only be formally classified as VUS. In addition, there is a case report (PMID 35252561) of a man presenting with no CP but spastic paraparesis and only slow disease progression in adult life (patient 48 years old at time of presentation). PMID 36085396 provides a literature review of described PCD2D patients, 72.7% of which have presented with spastic or dystonic quadriplegia, so there is significant phenotypic overlap with CP. Sources: Literature |
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| Cerebral Palsy v1.133 | PRUNE1 |
Luisa Weiss gene: PRUNE1 was added gene: PRUNE1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PRUNE1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRUNE1 were set to 33528536; 35379233 Phenotypes for gene: PRUNE1 were set to Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MIM#617481 Review for gene: PRUNE1 was set to GREEN Added comment: Case report of one consanguineous Iranian family with two children affected with spastic quadriplegic CP and a homozygous start loss of PRUNE1. The children also showed hypotonia and cerebellar atrophy. In addition, two additional cases in one large CP cohort study, one with homozygous mutation the other with compound heterozygous mutation/deletion. Sources: Literature |
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| Cerebral Palsy v1.54 | DYNC1H1 | Zornitza Stark Phenotypes for gene: DYNC1H1 were changed from Charcot-Marie-Tooth disease MIM#614228; Cortical dysplasia, complex MIM#614563; Spinal muscular atrophy, lower extremity-predominant MIM#158600 to Cortical dysplasia, complex MIM#614563 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.36 | DYNC1H1 |
Luisa Weiss gene: DYNC1H1 was added gene: DYNC1H1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: DYNC1H1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DYNC1H1 were set to 33528536; 25817843 Phenotypes for gene: DYNC1H1 were set to Charcot-Marie-Tooth disease MIM#614228; Cortical dysplasia, complex MIM#614563; Spinal muscular atrophy, lower extremity-predominant MIM#158600 Review for gene: DYNC1H1 was set to GREEN Added comment: Four patients with de novo heterozygous missense mutations and one patient with a de novo gene deletion in DYNC1H1 in two independent CP cohort studies described. Sources: Literature |
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| Cerebral Palsy v1.36 | BRAT1 |
Luisa Weiss gene: BRAT1 was added gene: BRAT1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: BRAT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BRAT1 were set to 29997391 Phenotypes for gene: BRAT1 were set to Neurodevelopmental disorder with cerebellar atrophy and with or without seizures MIM#618056; neonatal lethal rigidity and multifocal seizure syndrome MIM#614498 Review for gene: BRAT1 was set to AMBER Added comment: Biallelic BRAT1 mutations cause a neurodevelopmental phenotype with evidence of marked genotype–phenotype correlation: homozygous null variants result in a severe phenotype, whereas compound heterozygosity for null/hypomorphic variants is associated with a milder phenotype. In one study one patient with homozygous hypomorphic variants was diagnosed as a congenital cerebral palsy due to spastic paraplegia. Sources: Literature |
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| Cerebral Palsy v0.180 | SAMHD1 |
Chirag Patel gene: SAMHD1 was added gene: SAMHD1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SAMHD1 were set to PMID: 19525956 Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres syndrome 5; OMIM #612952 Review for gene: SAMHD1 was set to GREEN Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood. Rice et al. (2009) reported biallelic SAMHD1 mutations in 13 families with AGS. Sources: Literature |
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| Cerebral Palsy v0.178 | RNASEH2C |
Chirag Patel gene: RNASEH2C was added gene: RNASEH2C was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: RNASEH2C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2C were set to PMID: 17846997 Phenotypes for gene: RNASEH2C were set to Aicardi-Goutieres syndrome 3; OMIM #610329 Review for gene: RNASEH2C was set to GREEN Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood. Rice et al. (2007) reported biallelic RNASEH2C mutations in 18 families with AGS. Sources: Literature |
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| Cerebral Palsy v0.176 | RNASEH2A |
Chirag Patel gene: RNASEH2A was added gene: RNASEH2A was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: RNASEH2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2A were set to PMID: 17846997 Phenotypes for gene: RNASEH2A were set to Aicardi-Goutieres syndrome 4; OMIM #610333 Review for gene: RNASEH2A was set to GREEN Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood. Rice et al. (2007) reported biallelic RNASEH2A mutations in 3 families with AGS. Sources: Literature |
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| Cerebral Palsy v0.175 | RNASEH2B |
Chirag Patel gene: RNASEH2B was added gene: RNASEH2B was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2B were set to PMID: 17846997, 28762473 Phenotypes for gene: RNASEH2B were set to Aicardi-Goutieres syndrome 2; OMIM #610181 Review for gene: RNASEH2B was set to GREEN Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood. Rice et al. (2007) reported biallelic RNASEH2B mutations in 47 families with AGS. Svingen et al. (2017) reported 2 siblings with atypical AGS with spastic quadriplegia, anarthria, preserved intellect, and increased iron signal in basal ganglia and homozygous RNASEH2B pathogenic variant. Sources: Literature |
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| Cerebral Palsy v0.173 | TREX1 |
Chirag Patel gene: TREX1 was added gene: TREX1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TREX1 were set to PMID: 17846997, 33528536 Phenotypes for gene: TREX1 were set to Aicardi-Goutieres syndrome 1, dominant and recessive, OMIM #225750 Review for gene: TREX1 was set to GREEN Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood. Rice et al. (2007) reported biallelic TREX1 mutations in 31 families with AGS, and de novo heterozygous TREX1 mutation in 1 patient with AGS. Moreno-De-Luca et al. (2021) reported 1 patient with CP and paternally inherited pathogenic variant. Sources: Literature |
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| Cerebral Palsy v0.168 | SPTAN1 |
Chirag Patel gene: SPTAN1 was added gene: SPTAN1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPTAN1 were set to PMID: 20493457, 33528536, 34364746 Phenotypes for gene: SPTAN1 were set to Developmental and epileptic encephalopathy 5; OMIM #613477 Review for gene: SPTAN1 was set to GREEN Added comment: Developmental and epileptic encephalopathy-5 (DEE5) is a neurologic disorder characterised by tonic seizures/infantile spasms in first months of life, global developmental delay, lack of visual attention, poor head control, feeding difficulties, microcephaly, and spastic quadriplegia. Brain imaging may show cerebral atrophy and hypomyelination. Saitsu et al (2010) reported 2 patients with de novo in-frame mutations of SPTAN1 with early-onset WS with spastic quadriplegia, poor visual attention, and severe developmental delay. Moreno-De-Luca et al (2021) reported 3 patients with CP with de novo LP/P variants. Zahrani et al (2021) reported 1 patient with NDD (CP features) with de novo LP variant Sources: Literature |
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| Cerebral Palsy v0.140 | SPG11 |
Zornitza Stark gene: SPG11 was added gene: SPG11 was added to Cerebral Palsy. Sources: Expert list Mode of inheritance for gene: SPG11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPG11 were set to 34183250; 33581793 Phenotypes for gene: SPG11 were set to Spastic paraplegia 11, autosomal recessive, MIM# 604360 Review for gene: SPG11 was set to GREEN Added comment: Intellectual disability and spasticity, reported in CP cohort. Recent review of >300 individuals with SPG11-related disease. Mean age at onset was 13.10 ± 3.65 years, with initial symptoms like gait disturbance (107/195, 54.87%) and intellectual disability (47/195, 24.10%). Cognitive decline (228/270, 84.44%) was the most common complex manifestation stepped by dysarthria (134/195, 68.72%), neuropathy (112/177, 63.28%), amyatrophy, sphincter disturbance (60/130, 46.15%) and ataxia (90/194, 46.39%). Sources: Expert list |
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| Cerebral Palsy v0.89 | ATRX | Zornitza Stark Marked gene: ATRX as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.89 | ATRX | Zornitza Stark Gene: atrx has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.89 | ATRX | Zornitza Stark Classified gene: ATRX as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.89 | ATRX | Zornitza Stark Gene: atrx has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.88 | ATRX |
Zornitza Stark gene: ATRX was added gene: ATRX was added to Cerebral Palsy. Sources: Expert Review Mode of inheritance for gene: ATRX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ATRX were set to Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580 Review for gene: ATRX was set to GREEN Added comment: ID and hypotonia/hypertonia/spasticity: phenotypic overlap with CP. Well established gene-disease association. Sources: Expert Review |
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| Cerebral Palsy v0.55 | MINPP1 |
Zornitza Stark gene: MINPP1 was added gene: MINPP1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MINPP1 were set to 33257696 Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia Review for gene: MINPP1 was set to GREEN Added comment: 8 individuals from 6 unrelated families reported with bi-allelic LOF variants. All presented with almost complete absence of motor and cognitive development, progressive or congenital microcephaly, spastic tetraplegia or dystonia, and vision impairments. For most, the first symptoms included neonatal severe axial hypotonia and epilepsy that started during the first months or years of life. Prenatal symptoms of microcephaly associated with increased thalami echogenicity were detected in one, while the seven other individuals presented with progressive microcephaly. Some exhibited rapidly progressive phenotype and the affected children died in their infancy or middle-childhood. Strikingly, all the affected children had a unique brain MRI showing a mild to severe PCH, fluid-filled posterior fossa, with dilated lateral ventricles. In addition, severe atrophy at the level of the basal ganglia or thalami often associated with typical T2 hypersignal were identified in all the patients MRI. Supportive functional data showing accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions. Sources: Literature |
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| Cerebral Palsy v0.43 | ALK |
Dean Phelan gene: ALK was added gene: ALK was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ALK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ALK were set to PMID: 32989326 Phenotypes for gene: ALK were set to Spastic-dystonic diplegia Review for gene: ALK was set to AMBER Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two patients with spastic diplegia with mild tremor, scattered subcortical hyperintensities and an atrial septal defect; and spastic-dystonic diplegia, white matter abnormalities and epilepsy, respectively, with no evidence of neuroblastoma in either patient. Sources: Literature |
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