Phenotypic spectrum associated with de novo mutations in QRICH1 gene

Clin Genet. 2018 Feb;93(2):286-292. doi: 10.1111/cge.13096. Epub 2017 Dec 21.


Rare de novo mutations represent a significant cause of idiopathic developmental delay (DD). The use of next-generation sequencing (NGS) has boosted the identification of de novo mutations in an increasing number of novel genes. Here we present 3 unrelated children with de novo loss-of-function (LoF) mutations in QRICH1, diagnosed through trio-based exome sequencing. QRICH1 encodes the glutamine-rich protein 1, which contains 1 caspase activation recruitment domain and is likely to be involved in apoptosis and inflammation. All 3 children had speech delay, learning difficulties, a prominent nose and a thin upper lip. In addition, 2 of them had mildly raised creatine kinase (CK) and 1 of them had autism. Despite their small number, the patients had a relatively consistent pattern of clinical features suggesting the presence of a QRICH1-associated phenotype. LoF mutations in QRICH1 are suggested as a novel cause of DD.

Keywords: CK; QRICH1; autism; developmental delay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autistic Disorder / genetics*
  • Autistic Disorder / pathology
  • Child
  • Child, Preschool
  • Creatine Kinase
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / physiopathology
  • Exome / genetics
  • Female
  • Genetic Predisposition to Disease
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Infant
  • Infant, Newborn
  • Loss of Function Mutation
  • Male
  • Microtubule Proteins / genetics*
  • Mutation
  • Phenotype


  • Microtubule Proteins
  • QRICH2 protein, human
  • Creatine Kinase