Ke-Yan Qi1, Ming Shen2, Kai Yang1, You-Sheng Yan1, Jue Wu2, Yi-Peng Wang1, Cheng-Hong Yin1. 1. Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing 100026, China. 2. Research Center for Translational Medicine Laboratory, Medical Innovation Research Division of Chinese PLA General Hospital Beijing 100000, China.
Abstract
BACKGROUND: Turnpenny-Fry syndrome (TPFS) has recently been defined as an uncommon monogenic disease and is characterized by global developmental delay (GDD), intellectualdisability (ID), facial dysmorphology, and skeletal abnormality. PCGF2 is the only known causative gene for TPFS, which is a component of polycomb repressive complex 1 (PRC1). PRC1 is a multi-protein complex controlling the knockdown of gene expression. METHODS: The present study included the clinical evaluation of a 2.5-year-old boy with GDD and ID using cerebral MRI and the genetic testing with whole-exome sequencing. Additionally, the in silico molecular dynamic (MD) simulation was carried out on the identified variant. RESULTS: A recurrent missense variant, namely PCGF2: c.194C > T (p.Pro65Leu), was identified and suggested to be inherited from a mosaic father based on Sanger sequencing validation. MD results suggested a deleterious effect on the intramolecular structural flexibility and stability of PCGF2 protein by this variant. CONCLUSION: Our results indicated that PCGF2: p.Pro65Leu might be a hotspot for GDD and highlighted the effect of this variant on protein function. AJTR
BACKGROUND: Turnpenny-Fry syndrome (TPFS) has recently been defined as an uncommon monogenic disease and is characterized by global developmental delay (GDD), intellectualdisability (ID), facial dysmorphology, and skeletal abnormality. PCGF2 is the only known causative gene for TPFS, which is a component of polycomb repressive complex 1 (PRC1). PRC1 is a multi-protein complex controlling the knockdown of gene expression. METHODS: The present study included the clinical evaluation of a 2.5-year-old boy with GDD and ID using cerebral MRI and the genetic testing with whole-exome sequencing. Additionally, the in silico molecular dynamic (MD) simulation was carried out on the identified variant. RESULTS: A recurrent missense variant, namely PCGF2: c.194C > T (p.Pro65Leu), was identified and suggested to be inherited from a mosaic father based on Sanger sequencing validation. MD results suggested a deleterious effect on the intramolecular structural flexibility and stability of PCGF2 protein by this variant. CONCLUSION: Our results indicated that PCGF2: p.Pro65Leu might be a hotspot for GDD and highlighted the effect of this variant on protein function. AJTR
Authors: Nilah M Ioannidis; Joseph H Rothstein; Vikas Pejaver; Sumit Middha; Shannon K McDonnell; Saurabh Baheti; Anthony Musolf; Qing Li; Emily Holzinger; Danielle Karyadi; Lisa A Cannon-Albright; Craig C Teerlink; Janet L Stanford; William B Isaacs; Jianfeng Xu; Kathleen A Cooney; Ethan M Lange; Johanna Schleutker; John D Carpten; Isaac J Powell; Olivier Cussenot; Geraldine Cancel-Tassin; Graham G Giles; Robert J MacInnis; Christiane Maier; Chih-Lin Hsieh; Fredrik Wiklund; William J Catalona; William D Foulkes; Diptasri Mandal; Rosalind A Eeles; Zsofia Kote-Jarai; Carlos D Bustamante; Daniel J Schaid; Trevor Hastie; Elaine A Ostrander; Joan E Bailey-Wilson; Predrag Radivojac; Stephen N Thibodeau; Alice S Whittemore; Weiva Sieh Journal: Am J Hum Genet Date: 2016-09-22 Impact factor: 11.025