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| Mendeliome v1.3381 | MDGA2 |
Sangavi Sivagnanasundram changed review comment from: Affected individuals present with a broad neurodevelopmental impairment phenotype. Pre-print - https://doi.org/10.1101/2025.08.28.25330873 Individuals with developmental and epileptic encephalopathy (DEE) 8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features. 7 different biallelic LoF variants were identified p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1 In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism. PMID: 40168357, 27608760 A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment). The mice also showed abnormalities in excitatory synapses. Sources: Other; to: Affected individuals present with a broad neurodevelopmental impairment-like phenotype. Pre-print - https://doi.org/10.1101/2025.08.28.25330873 Individuals with developmental and epileptic encephalopathy (DEE) 8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features. 7 different biallelic LoF variants were identified p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1 In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism. PMID: 40168357, 27608760 A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment). The mice also showed abnormalities in excitatory synapses. Sources: Other |
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| Mendeliome v1.3381 | MDGA2 |
Sangavi Sivagnanasundram gene: MDGA2 was added gene: MDGA2 was added to Mendeliome. Sources: Other Mode of inheritance for gene: MDGA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MDGA2 were set to https://doi.org/10.1101/2025.08.28.25330873; 40168357; 27608760 Phenotypes for gene: MDGA2 were set to MDGA2-related neurodevelopmental disorder MONDO:0700092 Review for gene: MDGA2 was set to GREEN Added comment: Affected individuals present with a broad neurodevelopmental impairment phenotype. Pre-print - https://doi.org/10.1101/2025.08.28.25330873 Individuals with developmental and epileptic encephalopathy (DEE) 8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features. 7 different biallelic LoF variants were identified p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1 In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism. PMID: 40168357, 27608760 A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment). The mice also showed abnormalities in excitatory synapses. Sources: Other |
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