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| Hereditary Spastic Paraplegia - paediatric v1.85 | INPP4A |
Chirag Patel gene: INPP4A was added gene: INPP4A was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: INPP4A were set to PMID: 39315527 Phenotypes for gene: INPP4A were set to INPP4A-related neurodevelopmental disorder Review for gene: INPP4A was set to GREEN Added comment: PMID: 39315527 30 individuals (aged 6 months to 40 years) from 17 unrelated families with biallelic LOF variants in INPP4A gene (11 nonsense or frameshift and 3 missense, mostly exon 4). Cardinal clinical features include: severe global developmental delay, profound speech impairment, severe-profound intellectual disability, and severe lower limb weakness/paralysis. More variable clinical features include: microcephaly, short stature, cerebellar signs, involuntary movements, axial hypotonia, spasticity, quadriparesis, joint contractures, seizures, visual impairment. Neuroimaging findings vary from normal to features of (ponto)cerebellar hypoplasia, ventriculomegaly, reduced cerebral volume and hypomyelination. A more severe presentation is seen with variants downstream of exon 4. Preliminary fibroblast cell studies identify disruption of endocytic pathways as the likely mechanism of disease, consistent with previous findings of a role of INPP4A in endocytosis. All mouse models display a phenotype mirroring human INPP4A-related neurodevelopmental disorder entailing a severe movement disorder with inability to walk, a small brain, and poor growth/weight gain. Sources: Literature |
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| Hereditary Spastic Paraplegia - paediatric v0.176 | CYP2U1 | Zornitza Stark changed review comment from: SPG56 is an autosomal recessive neurodegenerative disorder characterized by early-onset progressive lower-limb spasticity resulting in walking difficulties. Upper limbs are often also affected, and some patients may have a subclinical axonal neuropathy. Onset is typically in the first decade.; to: SPG56 is an autosomal recessive neurodegenerative disorder characterized by early-onset progressive lower-limb spasticity resulting in walking difficulties. Upper limbs are often also affected, and some patients may have a subclinical axonal neuropathy. Onset is typically in the first decade. More than 5 unrelated families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.156 | ALK | Zornitza Stark Marked gene: ALK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.156 | ALK | Zornitza Stark Gene: alk has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.156 | ALK | Zornitza Stark Classified gene: ALK as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.156 | ALK | Zornitza Stark Gene: alk has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.155 | ALK |
Dean Phelan gene: ALK was added gene: ALK was added to Hereditary Spastic Paraplegia - paediatric. 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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| Hereditary Spastic Paraplegia - paediatric v0.134 | SARS2 |
Zornitza Stark gene: SARS2 was added gene: SARS2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature Mode of inheritance for gene: SARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SARS2 were set to 27279129 Phenotypes for gene: SARS2 were set to Progressive spastic paraplegia Review for gene: SARS2 was set to RED Added comment: Single individual reported with homozygous splicing mutation in SARS2 and with progressive spastic paresis rather than HUPRA syndrome (hyperuricemia, pulmonary hypertension, renal failure in infancy, and alkalosis) which is generally associated with missense variants in this gene. Sources: Literature |
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