Case Reports Am J Med Genet A

. 2019 Aug;179(8):1637-1641. doi: 10.1002/ajmg.a.61262. Epub 2019 Jun 17. https://pubmed.ncbi.nlm.nih.gov/31207137/

Expanding the phenotypic spectrum associated with DPF2: A new case report

Karen M Knapp ¹, Gemma Poke ², Danielle Jenkins ¹, Werner Truter ³, Louise S Bicknell ¹Affiliations expand

• PMID: 31207137
• DOI: 10.1002/ajmg.a.61262

Abstract

Coffin-Siris syndrome (CSS) is a clinically and genetically heterogeneous developmental disorder, linked to disruption of the BAF chromatin-remodeling complex. Recently, de novo missense and truncating variants have been reported in DPF2 in patients sharing some of the common features of CSS. Here we report a further individual harboring a novel de novo missense DPF2 variant, c.1066T>G, p.Cys356Gly. Structural modeling indicated that the predicted amino acid substitution affects a core residue required for zinc ion coordination and would likely alter the PHD2 domain structure of DPF2. The clinical presentation of Pierre Robin sequence and diaphragmatic hernia did not immediately suggest CSS, with the more common CSS features of hypoplastic toenails and characteristic facial features very subtle. This individual further broadens the phenotypic features of DPF2-related CSS, as well as CSS more generally.

Keywords: Coffin-Siris syndrome; clinical genetics; developmental disorders; exome sequencing.

© 2019 Wiley Periodicals, Inc.