title: The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non-syndromic mental retardation.
abstract: BACKGROUND
  The molecular basis of autosomal recessive non-syndromic mental retardation (NSMR) is poorly understood, mostly owing to heterogeneity and absence of clinical criteria for grouping families for linkage analysis. Only two autosomal genes, the PRSS12 gene on chromosome 4q26 and the CRBN on chromosome 3p26, have been shown to cause autosomal recessive NSMR, each gene in only one family.
  
  
  OBJECTIVE
  To identify the gene causing autosomal recessive NSMR on chromosome 19p13.12.
  
  
  RESULTS
  The candidate region established by homozygosity mapping was narrowed down from 2.4 Mb to 0.9 Mb on chromosome 19p13.12. A protein truncating mutation was identified in the gene CC2D1A in nine consanguineous families with severe autosomal recessive NSMR. The absence of the wild type protein in the lymphoblastoid cells of the patients was confirmed. CC2D1A is a member of a previously uncharacterised gene family that carries two conserved motifs, a C2 domain and a DM14 domain. The C2 domain is found in proteins which function in calcium dependent phospholipid binding; the DM14 domain is unique to the CC2D1A protein family and its role is unknown. CC2D1A is a putative signal transducer participating in positive regulation of I-kappaB kinase/NFkappaB cascade. Expression of CC2D1A mRNA was shown in the embryonic ventricular zone and developing cortical plate in staged mouse embryos, persisting into adulthood, with highest expression in the cerebral cortex and hippocampus.
  
  
  CONCLUSIONS
  A previously unknown signal transduction pathway is important in human cognitive development.
authors: Department of Medical Genetics, Rabin Medical Centre, Beilinson Campus, Petah Tikva 49100, Israel. basel@post.tau.ac.il
authors: L
authors: L
authors: Basel-Vanagaite
authors: R
authors: R
authors: Attia
authors: M
authors: M
authors: Yahav
authors: R J
authors: RJ
authors: Ferland
authors: L
authors: L
authors: Anteki
authors: C A
authors: CA
authors: Walsh
authors: T
authors: T
authors: Olender
authors: R
authors: R
authors: Straussberg
authors: N
authors: N
authors: Magal
authors: E
authors: E
authors: Taub
authors: V
authors: V
authors: Drasinover
authors: A
authors: A
authors: Alkelai
authors: D
authors: D
authors: Bercovich
authors: G
authors: G
authors: Rechavi
authors: A J
authors: AJ
authors: Simon
authors: M
authors: M
authors: Shohat
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D002893:Chromosomes, Human, Pair 3; D002894:Chromosomes, Human, Pair 4; D003071:Cognition; D003241:Consanguinity; D004268:DNA-Binding Proteins / Q000235:genetics*; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D005810:Multigene Family; D010447:Peptide Hydrolases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C512283:CC2D1A protein, human; C502543:CRBN protein, human; D004268:DNA-Binding Proteins; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases