Activity
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| Childhood onset hereditary spastic paraplegia v8.8 | INPP4A | Achchuthan Shanmugasundram Classified gene: INPP4A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v8.8 | INPP4A | Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (10 patients from 9 families and functional studies) for the promotion of this gene to green rating in the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v8.8 | INPP4A | Achchuthan Shanmugasundram Gene: inpp4a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v8.7 | INPP4A |
Achchuthan Shanmugasundram gene: INPP4A was added gene: INPP4A was added to Childhood onset hereditary spastic paraplegia. Sources: Literature Q3_25_promote_green tags were added to gene: INPP4A. Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: INPP4A were set to 39315527; 40748307; 40772914 Phenotypes for gene: INPP4A were set to neurodevelopmental disorder, MONDO:0700092 Review for gene: INPP4A was set to GREEN Added comment: PMID:39315527 (2025) reported 30 patients from 17 unrelated families with biallelic INPP4A variants and a clinically variable neurodevelopmental disorder. The clinical features include global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs, and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures, and cortical visual impairment. Nine patients from eight families were reported with spasticity, of which six had LoF variants downstream of exon 4 and the remaining three had missense variants. Although age of onset was not provided for these patients, the age of last examination for eight of nine patients were below 16. There is also functional evidence available in support of the disease association. Preliminary fibroblast cell lines from an affected individual showed disruption of endocytic pathways as the likely mechanism of disease. All mouse models displayed a phenotype mirroring human INPP4A-related neurodevelopmental disorder. PMID:40772914 (2025) reported a 34-month old female patient with the same biallelic variant that was reported in family 7 from PMID:39315527 (c.981del/ p.Asp328Ilefs*4) and with INPP4A-related disorder. This patient had spasticity. Sources: Literature |
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