A novel mutation in EED associated with overgrowth

• Published in: Journal of human genetics Vol. 60; no. 6; pp. 339 - 342
• Main Authors: Cohen, Ana S A, Tuysuz, Beyhan, Shen, Yaoqing, Bhalla, Sanjiv K, Jones, Steven J M, Gibson, William T
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-06-2015
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Adult; Congenital Hypothyroidism - diagnosis; Congenital Hypothyroidism - genetics; Craniofacial Abnormalities - diagnosis; Craniofacial Abnormalities - genetics; Diagnosis, Differential; DNA Mutational Analysis; Gene silencing; Growth Disorders - diagnosis; Growth Disorders - genetics; Hand Deformities, Congenital - diagnosis; Hand Deformities, Congenital - genetics; Humans; Male; Mutation; Mutation, Missense; Phenotypes; Polycomb group proteins; Polycomb Repressive Complex 2 - genetics
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/jhg.2015.26

In a patient suspected clinically to have Weaver syndrome, we ruled out mutations in EZH2 and NSD1, then identified a previously undescribed de novo mutation in EZH2's partner protein EED. Both proteins are members of the Polycomb Repressive Complex 2 that maintains gene silencing. On the basis of the similarities of the patient's phenotype to Weaver syndrome, which is caused by de novo mutations in EZH2, and on other lines of evidence including mouse Eed hypomorphs, we characterize this mutation as probably pathogenic for a Weaver-like overgrowth syndrome. This is the first report of overgrowth and related phenotypes associated with a constitutional mutation in human EED.