Elucidating the Genetic Landscape, Phenotypic Spectrum, and Pathogenic Mechanisms in a Turkish Cohort with Primary Microcephaly.

Genetic heterogeneity; mitotic/DNA pathways (MCPH) vs transcription/trafficking (syndromic PM)

A cohort of 87 patients from 64 Turkish families with primary hereditary microcephaly (MCPH) or syndromic primary microcephaly (PM) was characterized by exome sequencing. Overall diagnostic yield was 53.1%, with 83.7% biallelic variants and 52% consanguineous parents. Among 34 identified disease-causing variants, 15 were novel. MCPH genes involve mitotic division and DNA repair pathways, while syndromic PM genes involve transcriptional regulation and cell trafficking. A potential new candidate gene, KNTC1, was identified.

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

The 53% yield in this consanguineous cohort reflects exome's advantage for biallelic variants. The pathomechanistic distinction between MCPH (mitosis/DNA) and syndromic PM (transcription/trafficking) is pedagogically clear. KNTC1 as candidate gene warrants confirmation in independent cohorts.

Clinical impact: 2/3 · Evidence quality: 1/3 · Novelty: 1/2 · Sample size: 1/1 · Journal quality: 0/1 → Total: 5/10