Premium
Homozygous variants in the gene SCAPER cause syndromic intellectual disability
Author(s) -
Kahrizi Kimia,
Huber Mareike,
Galetzka Danuta,
Dewi Sri,
Schröder Julia,
Weis Eva,
Kariminejad Ariana,
Fattahi Zoherh,
Ropers HansHilger,
Schweiger Susann,
Najmabadi Hossein,
Winter Jennifer
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61172
Subject(s) - frameshift mutation , biology , genetics , nonsense , missense mutation , intellectual disability , gene , nonsense mediated decay , exon , loss function , mutation , rna splicing , rna , phenotype
The S‐Phase Cyclin A Associated Protein In The ER ( SCAPER ) gene is a ubiquitously expressed gene with unknown function in the brain. Recently, biallelic SCAPER variants were described in four patients from three families with retinitis pigmentosa (RP) and intellectual disability (ID). Here, we expand the spectrum of pathogenic variants in SCAPER and report on 10 further patients from four families with ID, RP, and additional dysmorphic features carrying homozygous variants in SCAPER . The variants found comprise frameshift, nonsense, and missense variants as well as an intragenic homozygous deletion, which spans SCAPER exons 15 and 16 and introduces a frameshift and a premature stop codon. Analyses of SCAPER expression in human and mouse brain revealed an upregulation of SCAPER expression during cortical development and a higher expression of SCAPER in neurons compared to neural progenitors. In the adult brain SCAPER is expressed in several regions including the cerebral cortex where it shows a layer‐specific expression with an expression peak in lower layer glutamatergic neurons. Our study supports the role of SCAPER variants in the pathogenesis of ID and RP, expands the variant spectrum and highlights the need for functional studies concerning the role of SCAPER during brain development and function.