Domain specific phenotypic expansion associated with variants in <i>MACF1</i>.

ABSTRACT:

Purpose

While heterozygous de novo missense variants in the microtubule-binding GAR domain of Microtubule-actin cross-linking factor 1 (MACF1) cause Lissencephaly 9 with Complex Brainstem Malformations [MIM #618325], the phenotypic impact of variants outside this domain remains unclear.

Methods

Through collaborative efforts, we assembled a cohort of 10 affected individuals from 8 unrelated families with either biallelic or monoallelic non-GAR domain MACF1 variants who exhibit partially overlapping yet unique phenotypic traits. Combined with previously reported cases, we analyzed genotype and phenotype data from 29 individuals using Human Phenotype Ontology (HPO)-based unsupervised hierarchical clustering.

Results

Clustering revealed two distinct p

SUBMITTER: Gogate N 

PROVIDER: S-EPMC12262753 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature