title: CIT, a gene involved in neurogenic cytokinesis, is mutated in human primary microcephaly.
abstract: Autosomal recessive primary microcephaly (MCPH) is a static neurodevelopmental disorder characterized by congenital small head circumference and non-progressive intellectual disability without additional severe brain malformations. MCPH is a genetically heterogeneous disorder. Sixteen genes (MCPH1-MCPH16) have been discovered so far, mutations thereof lead to autosomal recessive primary microcephaly. In a family, segregating MCPH in an autosomal recessive manner, genome-wide homozygosity mapping mapped a disease locus to 16.9-Mb region on chromosome 12q24.11-q24.32. Following this, exome sequencing in three affected individuals of the family discovered a splice site variant (c.753+3A>T) in citron kinase (CIT) gene, segregating with the disorder in the family. CIT co-localizes to the midbody ring during cytokinesis, and its loss of expression results in defects in neurogenic cytokinesis in both humans and mice. Splice site variant in CIT, identified in this study, is predicted to abolish splice donor site. cDNA sequence of an affected individual showed retention of an intron next to the splice donor site. The study, presented here, revealed the first variant in the CIT causing MCPH in the family.
authors: Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunawwarah, Saudi Arabia. sbasit.phd@gmail.com.
authors: Sulman
authors: S
authors: Basit
authors: College of Medicine, Taibah University, Almadinah Almunawwarah, Saudi Arabia.
authors: Khalid M
authors: KM
authors: Al-Harbi
authors: Paediatric Neurology Department, King Abdullah Medical City-Madinah Maternity and Children Hospital, Almadinah Almunawwarah, Saudi Arabia.
authors: Sabri A M
authors: SA
authors: Alhijji
authors: Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunawwarah, Saudi Arabia.
authors: Alia M
authors: AM
authors: Albalawi
authors: Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunawwarah, Saudi Arabia.
authors: Essa
authors: E
authors: Alharby
authors: College of Medicine, Taibah University, Almadinah Almunawwarah, Saudi Arabia.
authors: Amr
authors: A
authors: Eldardear
authors: Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunawwarah, Saudi Arabia.|College of Applied Medical Science, Taibah University, Almadinah Almunawwarah, Saudi Arabia.
authors: Mohammed I
authors: MI
authors: Samman
mesh_terms: D000293:Adolescent; D000818:Animals; D002648:Child; D048749:Cytokinesis / Q000235:genetics; D059472:Exome / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D051379:Mice; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D012529:Saudi Arabia
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D022821:RNA Splice Sites; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases