Setleis syndrome due to inheritance of the 1p36.22p36.21 duplication: Evidence for lack of penetrance

Beom Hee Lee, Christos Kasparis, Brenden Chen, Hui Mei, Lisa Edelmann, Celia Moss, David D. Weaver, Robert J. Desnick

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)717-722
Number of pages6
JournalJournal of Human Genetics
Volume60
Issue number11
DOIs
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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