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| Malformations of cortical development v7.52 | FBXO31 | Ida Ertmanska Classified gene: FBXO31 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Malformations of cortical development v7.52 | FBXO31 | Ida Ertmanska Added comment: Comment on list classification: There are more than 3 unrelated cases reported in literature with a recurrent de novo heterozygous missense variant FBXO31 p.Asp334Asn, presenting with childhood-onset spasticity, dystonia, ID, and cerebral abnormalities on MRI (including CC hypoplasia and white matter abnormalities). There are 2 recessive pedigrees reported, where individuals presented solely with intellectual disability and dysmorphic features. Hence, this gene can be promoted to Green at the next GMS update, with MOI set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Malformations of cortical development v7.52 | FBXO31 | Ida Ertmanska Gene: fbxo31 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Malformations of cortical development v7.51 | FBXO31 |
Ida Ertmanska gene: FBXO31 was added gene: FBXO31 was added to Malformations of cortical development. Sources: Literature Q2_26_promote_green tags were added to gene: FBXO31. Mode of inheritance for gene: FBXO31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FBXO31 were set to 24623383; 32989326; 33675180; 35019165; 41640354; 41640354 Phenotypes for gene: FBXO31 were set to neurodevelopmental disorder, MONDO:0700092; ?Intellectual developmental disorder, autosomal recessive 45, OMIM:615979 Review for gene: FBXO31 was set to GREEN Added comment: MONOALLELIC CASES: PMID: 32989326 Jin et al., 2020 Report of 2 unrelated patients with the same de novo FBXO31 mutation 16:87367889:C:T, p.Asp334Asn. Disease onset was under age two years. F218-003 - Female, European, presented with spastic diplegia, as well as Esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus. F699-003 - Male, European, presented with spastic paraplegia, as well as Ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation. PMID: 33675180 Dzinovic et al., 2021 Report of a 9yo boy of Slovakian descent, with a de novo FBXO31 variant c.1000G>A (p.Asp334Asn) - trio WES. He presented with complex, non‐progressive movement‐disorder syndrome dominated by spasticity and dystonia. Brain MRI showed bilateral occipital and parietal white‐matter volume reduction, irregular white‐matter dysmyelination. Intellectual disability estimated at Moderate severity (no IQ assessment; loss of speech at the age of 1.5 years, receptive language disorder) FBXO31 p.Asp334Asn is not reported in gnomAD v4.1.0. Revel prediction is Uncertain (0.46). PMID: 41858232 Galaz-Montoya et al., 2026 4 additional probands reported, all with the de novo FBXO31 p.Asp334Asn heterozygous variant. Core phenotypes: "cerebral palsy" i.e. mix of spasticity, dystonia, and hypotonia; ID/GDD, and speech impairment. Age of onset: at birth or very early childhood. Brain MRI showed hypoplastic corpus callosum (3/4), ventriculomegaly (2/4), and white matter abnormalitites (2/4). Authors propose the monoallelic disorder could be called "Kruer syndrome". PMID: 41640354 Schierbaum et al., 2026 13yo patient with with spastic diplegia, ID, and abnormal brain MRI findings: "ears of the lynx", thin corpus callosum, and periventricular white matter changes. Trio WGS showed that he had a de novo FBXO31 NM_024735.5, c.1000G>A, p.(Asp334Asn) variant. BIALLELIC CASES: PMID: 24623383 Mir et al., 2014 Consanguineous Pakistani pedigree, FBXO31 p.(Cys283Asnfs*81) segregated with intellectual disability in a recessive manner. Method: autozygosity mapping, WES, Sanger seq. PMID: 35019165 Moudi et al., 2022 Iranian consanguineous pedigree, 2 sibs with a homozygous FBXO31 c.1532G>A, p.Arg511Gln variant (7 alleles in gnomAD v4.1.1, no homozygotes). Heterozygous family members not affected. Phenotype: moderate ID, developmental delay, dysmorphic facial features. FBXO31 is putatively linked to AR ?Intellectual developmental disorder, autosomal recessive 45, OMIM:615979 in OMIM (accessed 13th Apr 2026). Sources: Literature |
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