Complex cortical dysplasia with other brain malformations

Complex cortical dysplasia with other brain malformations (CDCBM) is a disorder of aberrant neuronal migration and disturbed axonal guidance. Patients exhibit mental retardation, strabismus combined with nystagmus, axial hypotonia, and spasticity. The severity of mental retardation ranged from mild to severe. Complex cortical malformations associated with mutations in tubulin and motor proteins of the kinesin genes has been reported.

Congenital malformation

(CDCBM1) TUBB3 [HSA:10381] [KO:K07375]
(CDCBM2) KIF5C [HSA:3800] [KO:K10396]
(CDCBM3) KIF2A [HSA:3796] [KO:K10393]
(CDCBM4) TUBG1 [HSA:7283] [KO:K10389]
(CDCBM5) TUBB2A [HSA:7280] [KO:K07375]
(CDCBM6) TUBB [HSA:203068] [KO:K07375]
(CDCBM7) TUBB2B [HSA:347733] [KO:K07375]
(CDCBM8) TUBA8 [HSA:51807] [KO:K07374]
(CDCBM9) CTNNA2 [HSA:1496] [KO:K05691]

PMID:25059107

Fallet-Bianco C, Laquerriere A, Poirier K, Razavi F, Guimiot F, Dias P, Loeuillet L, Lascelles K, Beldjord C, Carion N, Toussaint A, Revencu N, Addor MC, Lhermitte B, Gonzales M, Martinovich J, Bessieres B, Marcy-Bonniere M, Jossic F, Marcorelles P, Loget P, Chelly J, Bahi-Buisson N

Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly.

Acta Neuropathol Commun 2:69 (2014)
DOI:10.1186/2051-5960-2-69

PMID:24812067

Willemsen MH, Ba W, Wissink-Lindhout WM, de Brouwer AP, Haas SA, Bienek M, Hu H, Vissers LE, van Bokhoven H, Kalscheuer V, Nadif Kasri N, Kleefstra T

Involvement of the kinesin family members KIF4A and KIF5C in intellectual disability and synaptic function.

J Med Genet 51:487-94 (2014)
DOI:10.1136/jmedgenet-2013-102182

PMID:20829227

Poirier K, Saillour Y, Bahi-Buisson N, Jaglin XH, Fallet-Bianco C, Nabbout R, Castelnau-Ptakhine L, Roubertie A, Attie-Bitach T, Desguerre I, Genevieve D, Barnerias C, Keren B, Lebrun N, Boddaert N, Encha-Razavi F, Chelly J

Mutations in the neuronal ss-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects.

Hum Mol Genet 19:4462-73 (2010)
DOI:10.1093/hmg/ddq377

PMID:19896110

Abdollahi MR, Morrison E, Sirey T, Molnar Z, Hayward BE, Carr IM, Springell K, Woods CG, Ahmed M, Hattingh L, Corry P, Pilz DT, Stoodley N, Crow Y, Taylor GR, Bonthron DT, Sheridan E

Mutation of the variant alpha-tubulin TUBA8 results in polymicrogyria with optic nerve hypoplasia.

Am J Hum Genet 85:737-44 (2009)
DOI:10.1016/j.ajhg.2009.10.007

PMID:30013181

Schaffer AE, Breuss MW, Caglayan AO, Al-Sanaa N, Al-Abdulwahed HY, Kaymakcalan H, Yilmaz C, Zaki MS, Rosti RO, Copeland B, Baek ST, Musaev D, Scott EC, Ben-Omran T, Kariminejad A, Kayserili H, Mojahedi F, Kara M, Cai N, Silhavy JL, Elsharif S, Fenercioglu E, Barshop BA, Kara B, Wang R, Stanley V, James KN, Nachnani R, Kalur A, Megahed H, Incecik F, Danda S, Alanay Y, Faqeih E, Melikishvili G, Mansour L, Miller I, Sukhudyan B, Chelly J, Dobyns WB, Bilguvar K, Jamra RA, Gunel M, Gleeson JG

Biallelic loss of human CTNNA2, encoding alphaN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration.

Nat Genet 50:1093-1101 (2018)
DOI:10.1038/s41588-018-0166-0