An exome sequencing study of Moebius syndrome including atypical cases reveals an individual with CFEOM3A and a mutation.

TitleAn exome sequencing study of Moebius syndrome including atypical cases reveals an individual with CFEOM3A and a mutation.
Publication TypeJournal Article
Year of Publication2017
AuthorsPatel, RM, Liu, D, Gonzaga-Jauregui, C, Jhangiani, S, Lu, JT, V Sutton, R, Fernbach, SD, Azamian, M, White, L, Edmond, JC, Paysse, EA, Belmont, JW, Muzny, DM, Lupski, JR, Gibbs, RA, Lewis, RAlan, Lee, BH, Lalani, SR, Campeau, PM
JournalCold Spring Harb Mol Case Stud
Date Published2017 Mar
KeywordsChild, Child, Preschool, Cohort Studies, Exome, Exome Sequencing, Eye Diseases, Hereditary, Facial Paralysis, Female, Humans, Infant, Male, Malformations of Cortical Development, Mobius Syndrome, Muscular Diseases, Mutation, Ocular Motility Disorders, Ophthalmoplegia, Orbital Diseases, Pedigree, Tubulin

Moebius syndrome is characterized by congenital unilateral or bilateral facial and abducens nerve palsies (sixth and seventh cranial nerves) causing facial weakness, feeding difficulties, and restricted ocular movements. Abnormalities of the chest wall such as Poland anomaly and variable limb defects are frequently associated with this syndrome. Most cases are isolated; however, rare families with autosomal dominant transmission with incomplete penetrance and variable expressivity have been described. The genetic basis of this condition remains unknown. In a cohort study of nine individuals suspected to have Moebius syndrome (six typical, three atypical), we performed whole-exome sequencing to try to identify a commonly mutated gene. Although no such gene was identified and we did not find mutations in and , we found a de novo heterozygous mutation, p.E410K, in the gene encoding tubulin beta 3 class III (), in an individual with atypical Moebius syndrome. This individual was diagnosed with near-complete ophthalmoplegia, agenesis of the corpus callosum, and absence of the septum pellucidum. No substantial limb abnormalities were noted. Mutations in have been associated with complex cortical dysplasia and other brain malformations and congenital fibrosis of extraocular muscles type 3A (CFEOM3A). Our report highlights the overlap of genetic etiology and clinical differences between CFEOM and Moebius syndrome and describes our approach to identifying candidate genes for typical and atypical Moebius syndrome.

Alternate JournalCold Spring Harb Mol Case Stud
PubMed ID28299356
PubMed Central IDPMC5334472
Grant ListUM1 HG006542 / HG / NHGRI NIH HHS / United States
P01 HD070394 / HD / NICHD NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
F30 MH098571 / MH / NIMH NIH HHS / United States

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