Brain malformations and mutations in α‐ and β‐tubulin genes: a review of the literature and description of two new cases. (7th January 2014)

• Record Type: Journal Article
• Authors: Romaniello, Romina; Arrigoni, Filippo; Cavallini, Anna; Tenderini, Erika; Baschirotto, Cinzia; Triulzi, Fabio; Bassi, Maria‐Teresa; Borgatti, Renato
• Is Part Of: Developmental medicine & child neurology. Volume 56:Number 4(2014:Apr.)
• Page Start: 354
• Page End: 360
• Publication Date: 2014-01-07
• Subjects: Child development -- Periodicals; Pediatric neurology -- Periodicals; 616.8
• DOI: 10.1111/dmcn.12370
• Languages: English
• ISSNs: 0012-1622

Abstract

<abstract abstract-type="main" id="dmcn12370-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="dmcn12370-sec-0001" sec-type="section"> <title>Aim</title> <p>The aim of this study was to determine the frequency of mutations in tubulin genes (<italic>TUBB2B, TUBA1A, and TUBB3</italic>) in patients with malformations of cortical development (MCDs) of unknown origin.</p> </sec> <sec id="dmcn12370-sec-0002" sec-type="section"> <title>Method</title> <p>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 MCDs 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 (<italic>n</italic>=13); syndromic disease (<italic>n</italic>=10); congenital infection (<italic>n</italic>=14); pregnancy complicated by twin‐to‐twin transfusion syndrome (<italic>n</italic>=2); proven mutations in known genes (<italic>n</italic>=13); poor magnetic resonance imaging (MRI) quality, or lack of informed consent (<italic>n</italic>=25). A genetic analysis of the <italic>TUBA1A</italic>, <italic> TUBB2B</italic> and <italic>TUBB3</italic> 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 <italic>TUBB2B</italic> and <italic>TUBA1A</italic> genes were reviewed; clinical and neuroradiological findings were compared and discussed.</p> </sec> <sec id="dmcn12370-sec-0003" sec-type="section"> <title>Results</title> <p>Two novel heterozygous mutations were detected: a heterozygous mutation in exon 4 of the <italic>TUBA1A</italic> gene (c.1160C>T) in a 5‐year‐old female with microcephaly, severe intellectual disability, and absence of language, and a c.1080 _1084del CCTGAinsACATCTTC in exon 4 of the <italic>TUBB2B</italic> 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.</p> </sec> <sec id="dmcn12370-sec-0004" sec-type="section"> <title>Interpretation</title> <p>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.</p> </sec> </abstract>