Intragenic loss-of-function variants in transcription factors MAZ, FOXP1 and SIN3B in colobomatous microphthalmia. J Med Genet 2026 Feb 20;63(3):141-146
Date
12/04/2025Pubmed ID
41339071Pubmed Central ID
PMC12851817DOI
10.1136/jmg-2025-111125Scopus ID
2-s2.0-105023892453 (requires institutional sign-in at Scopus site)Abstract
Despite the identification of many genes involved in developmental eye phenotypes, a large percentage of families lack genetic diagnoses, suggesting novel mechanisms remain to be discovered. Large deletions of 16p11.2, 3p14 or 19p13.11 regions involving transcription factors MAZ, FOXP1 and SIN3B, correspondingly, along with other genes, have been previously reported in individuals with neurodevelopmental and variable other features, including ocular coloboma and/or microphthalmia; recently, intragenic variants in FOXP1 and SIN3B have also been shown to cause neurodevelopmental phenotypes, with developmental eye defects reported in a small number of individuals with FOXP1 variants. Through exome sequencing analysis we identified novel splicing variants in MAZ and SIN3B, and a recurrent nonsense allele in FOXP1 in unrelated families affected with colobomatous microphthalmia, all with predicted loss-of-function effects; additionally, we report two new families with coloboma and 16p11.2 genomic deletions including MAZ, one de novo and another inherited from an affected parent. These findings provide further support for a role for FOXP1 in structural eye phenotypes, expanding its spectrum to include colobomatous microphthalmia, and suggest a role for MAZ and SIN3B in human eye development and disease.
Author List
Seese SE, Reis LM, Schneider A, Bardakjian T, Semina EVAuthor
Elena V. Semina PhD Chief, Professor in the Ophthalmology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ChildChild, Preschool
Chromosomes, Human, Pair 16
Coloboma
DNA-Binding Proteins
Female
Forkhead Transcription Factors
Humans
Loss of Function Mutation
Male
Microphthalmos
Pedigree
Phenotype
Repressor Proteins
Sin3 Histone Deacetylase and Corepressor Complex
Transcription Factors
