Spectrum of clinical heterogeneity of β-tubulin TUBB5 gene mutations

I. Madrigal, R. Rabionet, M. I. Alvarez-Mora, A. Sanchez, L. Rodríguez-Revenga, Xavier P. Estivill, M. Mila

Research output: Contribution to journalArticle

Abstract

Microcephaly is a rare condition in which the occipitofrontal circumference in a child is more than two standard deviations below the mean of children of the same age and gender. It is mainly caused by genetic abnormalities that interfere with the growth of the cerebral cortex during early months of fetal development. We present a case of a 12 years old patient with microcephaly. To identify a possible genetic origin of the phenotype, we performed array CGH and exome sequencing in the patient. Exome sequencing revealed the presence of a de novo missense mutation in the TUBB5 gene (E401K). Mutations in the TUBB5 are mainly responsible for microcephaly but the clinical spectrum is wide, from patients with severe developmental delay, and the presence of different brain malformations, to patients with only slightly cognitive impairment and normal motor development. Our patient shows a milder phenotype than other patients carrying the same mutation. These differences in the clinical features suggest that other factors, presumably genetic or epigenetic, could be modulating clinical expressivity of TUBB5. It is therefore evident that more functional studies are needed to understand the pathology that underlies the clinical spectrum of tubulin associated disease states.

Original languageEnglish
Pages (from-to)12-17
Number of pages6
JournalGene
Volume695
DOIs
Publication statusPublished - 5 May 2019

Fingerprint

Tubulin
Microcephaly
Mutation
Genes
Exome
Phenotype
Clinical Pathology
Missense Mutation
Fetal Development
Epigenomics
Cerebral Cortex
Brain
Growth

Keywords

  • Exome sequencing
  • Intellectual disability
  • Microcephaly
  • TUBB5

ASJC Scopus subject areas

  • Genetics

Cite this

Madrigal, I., Rabionet, R., Alvarez-Mora, M. I., Sanchez, A., Rodríguez-Revenga, L., Estivill, X. P., & Mila, M. (2019). Spectrum of clinical heterogeneity of β-tubulin TUBB5 gene mutations. Gene, 695, 12-17. https://doi.org/10.1016/j.gene.2019.02.002

Spectrum of clinical heterogeneity of β-tubulin TUBB5 gene mutations. / Madrigal, I.; Rabionet, R.; Alvarez-Mora, M. I.; Sanchez, A.; Rodríguez-Revenga, L.; Estivill, Xavier P.; Mila, M.

In: Gene, Vol. 695, 05.05.2019, p. 12-17.

Research output: Contribution to journalArticle

Madrigal, I, Rabionet, R, Alvarez-Mora, MI, Sanchez, A, Rodríguez-Revenga, L, Estivill, XP & Mila, M 2019, 'Spectrum of clinical heterogeneity of β-tubulin TUBB5 gene mutations', Gene, vol. 695, pp. 12-17. https://doi.org/10.1016/j.gene.2019.02.002
Madrigal I, Rabionet R, Alvarez-Mora MI, Sanchez A, Rodríguez-Revenga L, Estivill XP et al. Spectrum of clinical heterogeneity of β-tubulin TUBB5 gene mutations. Gene. 2019 May 5;695:12-17. https://doi.org/10.1016/j.gene.2019.02.002
Madrigal, I. ; Rabionet, R. ; Alvarez-Mora, M. I. ; Sanchez, A. ; Rodríguez-Revenga, L. ; Estivill, Xavier P. ; Mila, M. / Spectrum of clinical heterogeneity of β-tubulin TUBB5 gene mutations. In: Gene. 2019 ; Vol. 695. pp. 12-17.
@article{68474c3d58954fb2b2340f27304bda4b,
title = "Spectrum of clinical heterogeneity of β-tubulin TUBB5 gene mutations",
abstract = "Microcephaly is a rare condition in which the occipitofrontal circumference in a child is more than two standard deviations below the mean of children of the same age and gender. It is mainly caused by genetic abnormalities that interfere with the growth of the cerebral cortex during early months of fetal development. We present a case of a 12 years old patient with microcephaly. To identify a possible genetic origin of the phenotype, we performed array CGH and exome sequencing in the patient. Exome sequencing revealed the presence of a de novo missense mutation in the TUBB5 gene (E401K). Mutations in the TUBB5 are mainly responsible for microcephaly but the clinical spectrum is wide, from patients with severe developmental delay, and the presence of different brain malformations, to patients with only slightly cognitive impairment and normal motor development. Our patient shows a milder phenotype than other patients carrying the same mutation. These differences in the clinical features suggest that other factors, presumably genetic or epigenetic, could be modulating clinical expressivity of TUBB5. It is therefore evident that more functional studies are needed to understand the pathology that underlies the clinical spectrum of tubulin associated disease states.",
keywords = "Exome sequencing, Intellectual disability, Microcephaly, TUBB5",
author = "I. Madrigal and R. Rabionet and Alvarez-Mora, {M. I.} and A. Sanchez and L. Rodr{\'i}guez-Revenga and Estivill, {Xavier P.} and M. Mila",
year = "2019",
month = "5",
day = "5",
doi = "10.1016/j.gene.2019.02.002",
language = "English",
volume = "695",
pages = "12--17",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier",

}

TY - JOUR

T1 - Spectrum of clinical heterogeneity of β-tubulin TUBB5 gene mutations

AU - Madrigal, I.

AU - Rabionet, R.

AU - Alvarez-Mora, M. I.

AU - Sanchez, A.

AU - Rodríguez-Revenga, L.

AU - Estivill, Xavier P.

AU - Mila, M.

PY - 2019/5/5

Y1 - 2019/5/5

N2 - Microcephaly is a rare condition in which the occipitofrontal circumference in a child is more than two standard deviations below the mean of children of the same age and gender. It is mainly caused by genetic abnormalities that interfere with the growth of the cerebral cortex during early months of fetal development. We present a case of a 12 years old patient with microcephaly. To identify a possible genetic origin of the phenotype, we performed array CGH and exome sequencing in the patient. Exome sequencing revealed the presence of a de novo missense mutation in the TUBB5 gene (E401K). Mutations in the TUBB5 are mainly responsible for microcephaly but the clinical spectrum is wide, from patients with severe developmental delay, and the presence of different brain malformations, to patients with only slightly cognitive impairment and normal motor development. Our patient shows a milder phenotype than other patients carrying the same mutation. These differences in the clinical features suggest that other factors, presumably genetic or epigenetic, could be modulating clinical expressivity of TUBB5. It is therefore evident that more functional studies are needed to understand the pathology that underlies the clinical spectrum of tubulin associated disease states.

AB - Microcephaly is a rare condition in which the occipitofrontal circumference in a child is more than two standard deviations below the mean of children of the same age and gender. It is mainly caused by genetic abnormalities that interfere with the growth of the cerebral cortex during early months of fetal development. We present a case of a 12 years old patient with microcephaly. To identify a possible genetic origin of the phenotype, we performed array CGH and exome sequencing in the patient. Exome sequencing revealed the presence of a de novo missense mutation in the TUBB5 gene (E401K). Mutations in the TUBB5 are mainly responsible for microcephaly but the clinical spectrum is wide, from patients with severe developmental delay, and the presence of different brain malformations, to patients with only slightly cognitive impairment and normal motor development. Our patient shows a milder phenotype than other patients carrying the same mutation. These differences in the clinical features suggest that other factors, presumably genetic or epigenetic, could be modulating clinical expressivity of TUBB5. It is therefore evident that more functional studies are needed to understand the pathology that underlies the clinical spectrum of tubulin associated disease states.

KW - Exome sequencing

KW - Intellectual disability

KW - Microcephaly

KW - TUBB5

UR - http://www.scopus.com/inward/record.url?scp=85061380960&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061380960&partnerID=8YFLogxK

U2 - 10.1016/j.gene.2019.02.002

DO - 10.1016/j.gene.2019.02.002

M3 - Article

VL - 695

SP - 12

EP - 17

JO - Gene

JF - Gene

SN - 0378-1119

ER -