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De Novo Mutations of RERE Cause a Genetic Syndrome with Features that Overlap Those Associated with Proximal 1p36 Deletions.

Abstract：

:Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are associated with developmental delay, intellectual disability, and defects involving the brain, eye, ear, heart, and kidney. Arginine-glutamic acid dipeptide repeats (RERE) is located in the proximal 1p36 critical region. RERE is a widely-expressed nuclear receptor coregulator that positively regulates retinoic acid signaling. Animal models suggest that RERE deficiency might contribute to many of the structural and developmental birth defects and medical problems seen in individuals with 1p36 deletion syndrome, although human evidence supporting this role has been lacking. In this report, we describe ten individuals with intellectual disability, developmental delay, and/or autism spectrum disorder who carry rare and putatively damaging changes in RERE. In all cases in which both parental DNA samples were available, these changes were found to be de novo. Associated features that were recurrently seen in these individuals included hypotonia, seizures, behavioral problems, structural CNS anomalies, ophthalmologic anomalies, congenital heart defects, and genitourinary abnormalities. The spectrum of defects documented in these individuals is similar to that of a cohort of 31 individuals with isolated 1p36 deletions that include RERE and are recapitulated in RERE-deficient zebrafish and mice. Taken together, our findings suggest that mutations in RERE cause a genetic syndrome and that haploinsufficiency of RERE might be sufficient to cause many of the phenotypes associated with proximal 1p36 deletions.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Fregeau B,Kim BJ,Hernández-García A,Jordan VK,Cho MT,Schnur RE,Monaghan KG,Juusola J,Rosenfeld JA,Bhoj E,Zackai EH,Sacharow S,Barañano K,Bosch DGM,de Vries BBA,Lindstrom K,Schroeder A,James P,Kulch P,Lalani SR,van

doi

10.1016/j.ajhg.2016.03.002

subject

Has Abstract

pub_date

2016-05-05 00:00:00

pages

963-970

issue

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(16)30037-4

journal_volume

pub_type

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De Novo Mutations of RERE Cause a Genetic Syndrome with Features that Overlap Those Associated with Proximal 1p36 Deletions.