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| Macrocephaly_Megalencephaly v0.137 | MAX |
Rylee Peters gene: MAX was added gene: MAX was added to Macrocephaly_Megalencephaly. Sources: Literature Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAX were set to 38141607 Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related Review for gene: MAX was set to AMBER Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain. Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae. Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc. Sources: Literature |
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| Macrocephaly_Megalencephaly v0.71 | MYCN |
Kristin Rigbye gene: MYCN was added gene: MYCN was added to Macrocephaly_Megalencephaly. Sources: Literature Mode of inheritance for gene: MYCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MYCN were set to 30573562 Phenotypes for gene: MYCN were set to Neurodevelopmental disorder with megalencephaly Mode of pathogenicity for gene: MYCN was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: MYCN was set to RED Added comment: Single report of a de novo missense p.T58M in an individual with a novel megalencephaly syndrome, a Japanese boy with an intellectual disability (ID), distinctive facies, megalencephaly, ventriculomegaly, hypoplastic corpus callosum, postnatal growth retardation, postaxial polydactyly and neuroblastoma. Biochemical and cell biology experiments revealed that the mutation renders MYCN resistant to proteolysis and may improperly potentiate cortical neuron proliferation. MYCN activity regulates granule neuron proliferation through induction of CCND1 and CCND2, and this syndrome was similar to CCND2 gene abnormalities that impart excessive protein stability cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. This residue is also frequently mutated in c-Myc in Burkitt’s lymphoma (also due to GoF by gene amplification), consistent with its functions in cell proliferation and differentiation. Sources: Literature |
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| Macrocephaly_Megalencephaly v0.0 | CCND2 |
Zornitza Stark gene: CCND2 was added gene: CCND2 was added to Macrocephaly/Megalencephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: CCND2 was set to Unknown |
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