Setleis Syndrome Due to Inheritance of the 1p36.22p36.21 Duplication: Evidence for Lack of Penetrance

Overview

Journal J Hum Genet

Specialty Genetics

Date 2015 Aug 28

PMID 26311541

Citations 3

Authors

Beom Hee Lee

Christos Kasparis

Brenden Chen

Hui Mei

Lisa Edelmann

Celia Moss

David D Weaver

Robert J Desnick

Affiliations

Soon will be listed here.

Abstract

Setleis syndrome, focal facial dermal dysplasia type III (FFDD3, MIM #227260), is characterized by scar-like bitemporal lesions and other ocular and facial dysmorphic features. The syndrome results from recessive mutations in the TWIST2 gene, encoding a basic helix-loop-helix transcription factor or de novo genomic duplication or triplication, which include 1.3 Mb at 1p36.22p36.21, or other yet undefined lesions, emphasizing the syndrome's genetic heterogeneity. Recently, three patients were reported with 1p36.22p36.21 duplications/triplication that had the characteristic FFDD3 features and developmental delay or intellectual disabilities. Here, we describe a male with this microduplication, and the typical FFDD3 phenotype, but normal intelligence. Notably, his duplication was inherited from his father who did not have any FFDD3 manifestations, indicating lack of penetrance of the 1p36.22p36.21 microduplication. These findings emphasize phenotypic heterogeneity of the 1p36.22p36.21 copy number variant and the importance of screening the parents of patients with the 1p36.22p36.21 copy number variant to determine whether the duplication/triplication is de novo or inherited, for informed reproductive and genetic counseling.

Citing Articles

Mechanisms of Regulation of the Gene by the TWIST2 and ADD1/SREBP1c Transcription Factors.

Casasnovas-Nieves J, Rodriguez Y, Franco H, Cadilla C Genes (Basel). 2023; 14(9).

PMID: 37761873 PMC: 10530651. DOI: 10.3390/genes14091733.

Expression Profiling Identifies TWIST2 Target Genes in Setleis Syndrome Patient Fibroblast and Lymphoblast Cells.

Crespo N, Torres-Bracero A, Renta J, Desnick R, Cadilla C Int J Environ Res Public Health. 2021; 18(4).

PMID: 33669496 PMC: 7922891. DOI: 10.3390/ijerph18041997.

Focal facial dermal dysplasia type 4: identification of novel CYP26C1 mutations in unrelated patients.

Lee B, Morice-Picard F, Boralevi F, Chen B, Desnick R J Hum Genet. 2017; 63(3):257-261.

PMID: 29263414 DOI: 10.1038/s10038-017-0375-x.

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