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Brain malformations and mutations in α ‐ and β ‐tubulin genes: a review of the literature and description of two new cases
Author(s) -
Romaniello Romina,
Arrigoni Filippo,
Cavallini Anna,
Tenderini Erika,
Baschirotto Cinzia,
Triulzi Fabio,
Bassi MariaTeresa,
Borgatti Renato
Publication year - 2014
Publication title -
developmental medicine and child neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.658
H-Index - 143
eISSN - 1469-8749
pISSN - 0012-1622
DOI - 10.1111/dmcn.12370
Subject(s) - intellectual disability , microcephaly , polymicrogyria , medicine , hypoplasia , pediatrics , pathology , genetics , magnetic resonance imaging , biology , radiology
Aim The aim of this study was to determine the frequency of mutations in tubulin genes ( TUBB 2B, TUBA 1A, and TUBB 3 ) in patients with malformations of cortical development ( MCD s) of unknown origin. Method In total, 79 out of 156 patients (41 males, 38 females; age range 8mo–55y (mean age 13y 3mo, SD 11y 2mo) with a neuroradiological diagnosis of MCD s were enrolled in the study. The 77 excluded patients were excluded for the following reasons: suspected or proven diagnosis of pre‐ or perinatal ischaemic insult ( n =13); syndromic disease ( n =10); congenital infection ( n =14); pregnancy complicated by twin‐to‐twin transfusion syndrome ( n =2); proven mutations in known genes ( n =13); poor magnetic resonance imaging ( MRI ) quality, or lack of informed consent ( n =25). A genetic analysis of the TUBA 1A , TUBB 2B and TUBB 3 genes was carried out by direct sequencing of the coding regions of the relevant genes for each participant. Previously described patients with mutations in the TUBB 2B and TUBA 1A genes were reviewed; clinical and neuroradiological findings were compared and discussed. Results Two novel heterozygous mutations were detected: a heterozygous mutation in exon 4 of the TUBA 1A gene (c.1160C>T) in a 5‐year‐old female with microcephaly, severe intellectual disability, and absence of language, and a c.1080 _1084del CCTGA ins ACATCTTC in exon 4 of the TUBB 2B gene in a 31‐year‐old female with microcephaly, spastic tetraparesis, severe intellectual disability, and scoliosis. Different types of cortical abnormalities, cerebellar vermis hypoplasia, and optic nerve hypoplasia/atrophy were detected on MRI . Dysmorphisms of the basal ganglia and the hippocampi with abnormalities of the midline commissural structures were present in both cases. Interpretation The consistent presence of hypoplastic and disorganized white matter tracts suggests that, in addition to defects in neuronal migration, disruption of axon growth and guidance is a peculiar feature of tubulin‐related disorders.