Identification of a syndrome comprising microcephaly and intellectual disability but not white matter disease associated with a homozygous c.676C>T p.R226W DEAF1 mutation. Issue 5 (2nd February 2016)

• Record Type: Journal Article
• Authors: Gund, Christian; Powis, Zöe; Alcaraz, Wendy; Desai, Sonal; Baranano, Kristin
• Is Part Of: American journal of medical genetics. Volume 170:Issue 5(2016)
• Page Start: 1330
• Page End: 1332
• Publication Date: 2016-02-02
• Subjects: DEAF1 protein -- human -- exome -- clinical diagnostic sequencing -- consanguinity -- microcephaly -- intellectual disability; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.37580
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : We evaluated a 13‐year‐old East Pakistani male affected with microcephaly, apparent intellectual disability, hypotonia, and brisk reflexes without spasticity. His parents were first cousins. The patient also had a brother who was similarly affected and died at 10 years due to an accident. Previous SNP array testing showed a 1.63 Mb duplication at 16p13.11 of uncertain significance along with regions of homozygosity. Exome sequencing identified a known pathogenic homozygous alteration in DEAF1, c.676C>T (p.R226W), in this patient. The alteration had been reported in two individuals from a consanguineous Saudi Arabian family. Both individuals had microcephaly, intellectual disability, hypotonia, feeding difficulties, and poor growth. The patient reported here did not have evidence of white matter disease, as had been reported with prior patients. We conclude that this DEAF1 gene alteration caused this patient's symptoms and that white matter disease should not be considered a obligate feature of this syndrome. © 2016 Wiley Periodicals, Inc.