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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.

SUBMITTER: Shinwari JM

PROVIDER: S-EPMC4289688 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Recessive mutations in COL25A1 are a cause of congenital cranial dysinnervation disorder.

Shinwari Jameela M A JM Khan Arif A Awad Salma S Shinwari Zakia Z Alaiya Ayodele A Alanazi Mohamad M Tahir Asma A Poizat Coralie C Al Tassan Nada N

American journal of human genetics 20141211 1

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 th ...[more]

PMID: 25500261

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