TY - JOUR
T1 - Whole-exome sequencing identifies a de novo TUBA1A mutation in a patient with sporadic malformations of cortical development
T2 - A case report
AU - Shimojima, Keiko
AU - Narita, Aya
AU - Maegaki, Yoshihiro
AU - Saito, Akira
AU - Furukawa, Toru
AU - Yamamoto, Toshiyuki
N1 - Publisher Copyright:
© 2014 Shimojima et al.; licensee BioMed Central Ltd.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014/7/22
Y1 - 2014/7/22
N2 - Background: Owing to the number of genetic mutations that contribute to malformations of cortical development, identification of causative mutations in candidate genes is challenging. To overcome these challenges, we performed whole-exome sequencing in this study. Case presentation. A Japanese patient presented with microcephaly and severe developmental delay. Brain magnetic resonance imaging showed the presence of colpocephaly associated with lateral ventricle dilatation and the presence of a simplified gyral pattern. Hypoplasia of the corpus callosum and cerebellar vermis were also noted. Because Sanger sequencing is expensive, laborious, and time-consuming, whole-exome sequencing was performed and a de novo missense mutation in TUBA1A (E27Q) was identified. Conclusion: The novel mutation identified in this study was located in the genetic region that encodes the N-terminal domain of TUBA1A, a region of TUBA1A with few reported mutations. Retrospective assessment of the clinical and radiological features of this patient i.e., microcephaly, lissencephaly (pachygyria) with cerebellar hypoplasia, and corpus callosum hypoplasia indicated that the TUBA1A mutation did not lead to any contradictions. Because rapid and comprehensive mutation analysis by whole-exome sequencing is time- and cost-effective, it might be useful for genetic counseling of patients with sporadic malformations of cortical development.
AB - Background: Owing to the number of genetic mutations that contribute to malformations of cortical development, identification of causative mutations in candidate genes is challenging. To overcome these challenges, we performed whole-exome sequencing in this study. Case presentation. A Japanese patient presented with microcephaly and severe developmental delay. Brain magnetic resonance imaging showed the presence of colpocephaly associated with lateral ventricle dilatation and the presence of a simplified gyral pattern. Hypoplasia of the corpus callosum and cerebellar vermis were also noted. Because Sanger sequencing is expensive, laborious, and time-consuming, whole-exome sequencing was performed and a de novo missense mutation in TUBA1A (E27Q) was identified. Conclusion: The novel mutation identified in this study was located in the genetic region that encodes the N-terminal domain of TUBA1A, a region of TUBA1A with few reported mutations. Retrospective assessment of the clinical and radiological features of this patient i.e., microcephaly, lissencephaly (pachygyria) with cerebellar hypoplasia, and corpus callosum hypoplasia indicated that the TUBA1A mutation did not lead to any contradictions. Because rapid and comprehensive mutation analysis by whole-exome sequencing is time- and cost-effective, it might be useful for genetic counseling of patients with sporadic malformations of cortical development.
KW - Lissencephaly
KW - Malformations of cortical development
KW - Microcephaly
KW - TUBA1A
KW - Whole-exome sequencing
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U2 - 10.1186/1756-0500-7-465
DO - 10.1186/1756-0500-7-465
M3 - Article
C2 - 25053001
AN - SCOPUS:84904531927
VL - 7
JO - BMC Research Notes
JF - BMC Research Notes
SN - 1756-0500
IS - 1
M1 - 465
ER -