Neurological segmental overgrowth
Gene: MAX
Comment on list classification: As reviewed by James Poulter, there is sufficient evidence available (three unrelated cases with the same p.Arg60Gln variant and functional studies) for the promotion of this gene to green rating in the next GMS update.Created: 18 Apr 2024, 7:43 p.m. | Last Modified: 18 Apr 2024, 7:43 p.m.
Panel Version: 2.12
PMID:38141607 reported three individuals with the same recurrent de novo germline variant in the MAX gene (p.Arg60Gln). 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.
This gene has been associated with relevant phenotypes in OMIM (MIM #620712).Created: 18 Apr 2024, 7:37 p.m. | Last Modified: 18 Apr 2024, 7:41 p.m.
Panel Version: 2.11
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Polydactyly-macrocephaly syndrome, OMIM:620712
Publications
Recurrent de novo variant (p.Arg60Gln) identified in 3 unrelated individuals. Pathogenicity supported by functional analysis.
Sources: LiteratureCreated: 7 Mar 2024, 9:48 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Macrocephaly; Polydactyly; delayed ophthalmic development; autism
Publications
Gene: max has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: MAX were changed from Macrocephaly; Polydactyly; delayed ophthalmic development; autism to Polydactyly-macrocephaly syndrome, OMIM:620712
Tag Q2_24_promote_green tag was added to gene: MAX. Tag Q2_24_NHS_review tag was added to gene: MAX.
Publications for gene: MAX were set to PMID:38141607
gene: MAX was added gene: MAX was added to Neurological segmental overgrowth. Sources: Literature Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAX were set to PMID:38141607 Phenotypes for gene: MAX were set to Macrocephaly; Polydactyly; delayed ophthalmic development; autism Penetrance for gene: MAX were set to Complete Review for gene: MAX was set to GREEN