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A de novo deletion in a boy with cerebral palsy suggests a refined critical region for the 4q21.22 microdeletion syndrome

Lookup NU author(s): Professor Jeremy Parr


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© 2017 Wiley Periodicals, Inc. We present an 18-year-old boy with cerebral palsy, intellectual disability, speech delay, and seizures. He carries a likely pathogenic 1.3Mb de novo heterozygous deletion in the 4q21.22 microdeletion syndrome region. He also carries a 436kb maternally-inherited duplication impacting the first three exons of CHRNA7. The majority of previously published cases with 4q21.22 syndrome shared common features including growth restriction, muscular hypotonia, and absent or severely delayed speech. Using copy number variation (CNV) data available for other subjects, we defined a minimal critical region of 170.8kb within the syndromic region, encompassing HNRNPD. We also identified a larger 2Mb critical region encompassing ten protein-coding genes, of which six (PRKG2, RASGEF1B, HNRNPDL, HNRNPD, LIN54, COPS4) have a significantly low number of truncating loss-of-function mutations. Long-range chromatin interaction data suggest that this deletion may alter chromatin interactions at the 4q21.22 microdeletion region. We suggest that the deletion or misregulation of these genes is likely to contribute to the neurodevelopmental and neuromuscular abnormalities in 4q21.22 syndrome.

Publication metadata

Author(s): Zarrei M, Merico D, Kellam B, Engchuan W, Scriver T, Jokhan R, Wilson MD, Parr J, Lemire EG, Stavropoulos DJ, Scherer SW

Publication type: Article

Publication status: Published

Journal: American Journal of Medical Genetics, Part A

Year: 2017

Volume: 173

Issue: 5

Pages: 1287-1293

Print publication date: 01/05/2017

Online publication date: 03/04/2017

Acceptance date: 18/01/2017

ISSN (print): 1552-4825

ISSN (electronic): 1552-4833

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/ajmg.a.38176


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