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| Genetic Epilepsy v0.2144 | PLP1 |
Lisa Norbart gene: PLP1 was added gene: PLP1 was added to Genetic Epilepsy. Sources: Literature Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: PLP1 were set to 7512350; 11071483; 21679407; 28133555; 29486744; 35346287; 37637647 Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher Disease, MIM#312080 Review for gene: PLP1 was set to GREEN Added comment: PMID: 7512350 (1994) - Mouse study demonstrating that seizures and convulsions are a result of a 2-fold increased PLP gene dosage. (Cited in OMIM) PMID: 11071483 (2000) - One family with 2x brothers affected with PMD, both developing seizures in late teens. Other symptoms in both brothers include hypotonia at birth, nystagmus, and slowly progressive spastic paraplegia. (Cited in OMIM) PMID: 21679407 (2011) - Male cohort, 43 individuals from 38 unrelated families with a PLP1-related disorder diagnosis. Seizures present in 2/43 males (both PLP1 duplication mutations). Additional symptoms include 3/43 stridor, 4/43 developmental delay, and 18/43 muscular hypotonia. PMID: 28133555 (2017) - Case report on 9 year old male affected with classic PMD. Presented with a history of seizures since age 4. Also presents with developmental delay, nystagmus, microcephaly, spastic quadriplegia. Maternally inherited gain of 436Kb on Xq22.2 encompassing TCEAL1,MORF4L2, PLP1, and RAB9B, of which only PLP1 is associated with a disease. PMID: 29486744 (2018) - Case report on family diagnosed with connatal PMD (previously diagnosed as X-linked epileptic seizures). The PLP1 missense mutation p.Ala84Asp was found to segregate in the family. 1x proband presenting with daily generalised seizures, onset at 8 months and no treatment response. 2x cousins and 2x maternal uncles also presented with epilepsy, all onset around 6 months and all died in childhood. Additional symptoms include 5/5 hypotonia and 5/5 psycho-motor delay. Consanguinity reported in the family. PMID: 35346287 (2022) - Chinese cohort of 141 patients, 111 whom were followed up with. Seizures present in 4/28 individuals with connatal PMD, including 1 patient who died due to epileptic seizures at age 7, and 4/56 individuals with transitional PMD. Additional symptoms include 111/111 development delay, 110/111 nystagmus, 93/111 hypotonia, 35/111 stridor, and 4/111 respiratory difficulty. PMID: 37637647 (2023) - Case report on 1x newborn individual diagnosed with failure to thrive and later PMD. Presented with episodes of rapid eye and side-to-side head movement episodes of 5-10 seconds, onset one month after birth. Diagnosis of seizure disorder considered before further testing. Individual hemizygous for PLP1: c.67G>A (p.Gly23Arg), maternally inherited. GeneReviews: Seizures may develop in infants affected by 'severe connatal PMD'. Sources: Literature |
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| Genetic Epilepsy v0.2019 | TCEAL1 | Belinda Chong reviewed gene: TCEAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36368327; Phenotypes: Neurodevelopmental disorder with gait disturbance, dysmorphic facies and behavioral abnormalities, X-linked, MIM# 301094; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.1830 | TCEAL1 | Zornitza Stark Phenotypes for gene: TCEAL1 were changed from Neurodevelopmental disorder, MONDO:0700092, TCEAL1-related hypotonia, abnormal gait, developmental delay, intellectual disability, autism, dysmorphic facial features. to Neurodevelopmental disorder with gait disturbance, dysmorphic facies and behavioral abnormalities, X-linked, MIM# 301094 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.1829 | TCEAL1 | Zornitza Stark reviewed gene: TCEAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with gait disturbance, dysmorphic facies and behavioral abnormalities, X-linked, MIM# 301094; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.1810 | TCEAL1 | Zornitza Stark Marked gene: TCEAL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.1810 | TCEAL1 | Zornitza Stark Gene: tceal1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.1810 | TCEAL1 | Zornitza Stark Classified gene: TCEAL1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.1810 | TCEAL1 | Zornitza Stark Gene: tceal1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.1809 | TCEAL1 | Melanie Marty edited their review of gene: TCEAL1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, TCEAL1-related, hypotonia, abnormal gait, developmental delay, intellectual disability, autism, dysmorphic facial features | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.1809 | TCEAL1 |
Melanie Marty gene: TCEAL1 was added gene: TCEAL1 was added to Genetic Epilepsy. Sources: Literature Mode of inheritance for gene: TCEAL1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: TCEAL1 were set to PMID: 36368327 Phenotypes for gene: TCEAL1 were set to Neurodevelopmental disorder, MONDO:0700092, TCEAL1-related hypotonia, abnormal gait, developmental delay, intellectual disability, autism, dysmorphic facial features. Review for gene: TCEAL1 was set to AMBER Added comment: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. 1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features. 4 PTCs, 2 CNVs, 2 missense reported. Only 2 individuals had seizures = amber for this panel at this stage. Sources: Literature |
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