title: Recessive mutations in COL25A1 are a cause of congenital cranial dysinnervation disorder.
abstract: Abnormal ocular motility is a common clinical feature in congenital cranial dysinnervation disorder (CCDD). To date, eight genes related to neuronal development have been associated with different CCDD phenotypes. By using linkage analysis, candidate gene screening, and exome sequencing, we identified three mutations in collagen, type XXV, alpha 1 (COL25A1) in individuals with autosomal-recessive inheritance of CCDD ophthalmic phenotypes. These mutations affected either stability or levels of the protein. We further detected altered levels of sAPP (neuronal protein involved in axon guidance and synaptogenesis) and TUBB3 (encoded by TUBB3, which is mutated in CFEOM3) as a result of null mutations in COL25A1. Our data suggest that lack of COL25A1 might interfere with molecular pathways involved in oculomotor neuron development, leading to CCDD phenotypes.
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Jameela M A
authors.initials: JM
authors.lastname: Shinwari
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia; Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, P.O. Box 7191, Riyadh 11462, Saudi Arabia.
authors.forename: Arif
authors.initials: A
authors.lastname: Khan
authors.affiliation: Cardiovascular Research Program, Research Center, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Salma
authors.initials: S
authors.lastname: Awad
authors.affiliation: Stem Cell and Tissue Engineering Program, Research Center, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Zakia
authors.initials: Z
authors.lastname: Shinwari
authors.affiliation: Stem Cell and Tissue Engineering Program, Research Center, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Ayodele
authors.initials: A
authors.lastname: Alaiya
authors.affiliation: Genome Research Chair, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Alanazi
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Asma
authors.initials: A
authors.lastname: Tahir
authors.affiliation: Cardiovascular Research Program, Research Center, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Coralie
authors.initials: C
authors.lastname: Poizat
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: naltassan@kfshrc.edu.sa.
authors.forename: Nada
authors.initials: N
authors.lastname: Al Tassan
mesh_terms: D002648:Child; D059472:Exome; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D009154:Mutation; D055495:Neurogenesis / Q000235:genetics; D024041:Non-Fibrillar Collagens / Q000235:genetics* / Q000378:metabolism; D015835:Ocular Motility Disorders / Q000235:genetics*; D015840:Oculomotor Nerve Diseases / Q000235:genetics*; D010641:Phenotype; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: C456021:COL25A1 protein, human; D024041:Non-Fibrillar Collagens; C498585:TUBB3 protein, human; D014404:Tubulin