A Novel MAP3K7 Variant Causing Loss of Function Identified in a Family With Cardiospondylocarpofacial Syndrome: Functional Validation and Molecular Insights

MAP3K7 (novel heterozygous LOF variant — TAK1)

Novel heterozygous LOF variant in MAP3K7/TAK1 + biochemical functional validation (WES + biochemical assays) — genotype-phenotype correlation

MAP3K7 (TAK1), a kinase involved in multiple cell signalling pathways, is associated with two distinct syndromes: frontometaphyseal dysplasia type 2 (FMD2, gain-of-function variants) and cardiospondylocarpofacial syndrome (CSCF, loss-of-function variants). The authors report a novel heterozygous LOF variant in MAP3K7 in a Chinese patient with CSCF and provide functional validation through WES and biochemical assays, refining the genotype-phenotype correlation between the two syndromes.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Useful reminder for interpretation: MAP3K7 LOF variants cause CSCF while GOF variants cause FMD2 — the variant nature (LOF vs GOF) determines the syndrome. To verify systematically during ACMG classification. An illustrative case with rigorous functional validation.

known gene +0; novel LOF variant +1; AD het +1; biochemical functional +2; 1 family +0; CSCF vs FMD2 G/P correlation +1; Hum Mutat +1