@article {1619431,
	title = {TUBB3 Arg262His causes a recognizable syndrome including CFEOM3, facial palsy, joint contractures, and early-onset peripheral neuropathy},
	journal = {Hum Genet},
	volume = {140},
	number = {12},
	year = {2021},
	month = {2021 Dec},
	pages = {1709-1731},
	abstract = {Microtubules are formed from heterodimers of alpha- and beta-tubulin, each of which has multiple isoforms encoded by separate genes. Pathogenic missense variants in multiple different tubulin isoforms cause brain malformations. Missense mutations in TUBB3, which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype-phenotype correlations. Here, we report fourteen individuals from thirteen unrelated families, each of whom harbors the identical NM_006086.4 (TUBB3):c.785G\&gt;A (p.Arg262His) variant resulting in a phenotype we refer to as the TUBB3 R262H syndrome. The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life. Subsets may also have vocal cord paralysis, auditory dysfunction, cyclic vomiting, and/or tachycardia at rest. All fourteen subjects share a recognizable set of brain malformations, including hypoplasia of the corpus callosum and anterior commissure, basal ganglia malformations, absent olfactory bulbs and sulci, and subtle cerebellar malformations. While similar, individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures, an earlier onset peripheral neuropathy, impaired gait, and basal ganglia malformations.},
	keywords = {Abnormalities, Multiple, Adolescent, Adult, Amino Acid Substitution, Arginine, Child, Child, Preschool, Facial Paralysis, Female, Fibrosis, Histidine, Humans, Infant, Male, Mutation, Ophthalmoplegia, Peripheral Nervous System Diseases, Syndrome, Tubulin, Young Adult},
	issn = {1432-1203},
	doi = {10.1007/s00439-021-02379-9},
	author = {Whitman, Mary C and Barry, Brenda J and Robson, Caroline D and Facio, Flavia M and Van Ryzin, Carol and Chan, Wai-Man and Lehky, Tanya J and Thurm, Audrey and Zalewski, Christopher and King, Kelly A and Brewer, Carmen and Almpani, Konstantinia and Lee, Janice S and Delaney, Angela and FitzGibbon, Edmond J and Lee, Paul R and Toro, Camilo and Paul, Scott M and Abdul-Rahman, Omar A and Webb, Bryn D and Jabs, Ethylin Wang and Moller, Hans Ulrik and Larsen, Dorte Ancher and Antony, Jayne H and Troedson, Christopher and Ma, Alan and Ragnhild, Glad and Wirgenes, Katrine V and Tham, Emma and Kvarnung, Malin and Maarup, Timothy James and MacKinnon, Sarah and Hunter, David G and Collins, Francis S and Manoli, Irini and Engle, Elizabeth C}
}
