Identification of two novel de novo TUBB variants in cases with brain malformations: case reports and literature review

doi:10.1038/s10038-021-00956-4

Review

. 2021 Dec;66(12):1193-1197.

doi: 10.1038/s10038-021-00956-4. Epub 2021 Jul 1.

Identification of two novel de novo TUBB variants in cases with brain malformations: case reports and literature review

Kazuki Watanabe¹, Mitsuko Nakashima², Satoko Kumada³, Hideaki Mashimo³, Mikako Enokizono⁴, Keitaro Yamada⁵, Mitsuhiro Kato⁶, Hirotomo Saitsu⁷

Affiliations

¹ Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
² Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan. mnakashi@hama-med.ac.jp.
³ Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.
⁴ Department of Radiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
⁵ Department of Pediatric Neurology, Aichi Developmental Disability Center Central Hospital, Kasugai, Japan.
⁶ Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
⁷ Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan. hsaitsu@hama-med.ac.jp.

PMID: 34211110
DOI: 10.1038/s10038-021-00956-4

Review

Identification of two novel de novo TUBB variants in cases with brain malformations: case reports and literature review

Kazuki Watanabe et al. J Hum Genet. 2021 Dec.

. 2021 Dec;66(12):1193-1197.

doi: 10.1038/s10038-021-00956-4. Epub 2021 Jul 1.

Authors

Kazuki Watanabe¹, Mitsuko Nakashima², Satoko Kumada³, Hideaki Mashimo³, Mikako Enokizono⁴, Keitaro Yamada⁵, Mitsuhiro Kato⁶, Hirotomo Saitsu⁷

Affiliations

¹ Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
² Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan. mnakashi@hama-med.ac.jp.
³ Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.
⁴ Department of Radiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
⁵ Department of Pediatric Neurology, Aichi Developmental Disability Center Central Hospital, Kasugai, Japan.
⁶ Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
⁷ Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan. hsaitsu@hama-med.ac.jp.

PMID: 34211110
DOI: 10.1038/s10038-021-00956-4

Abstract

Heterozygous variants in TUBB encoding one of β-tubulin isotypes are known to cause two overlapping developmental brain disorders, complex cortical dysplasia with other brain malformations (CDCBM) and congenital symmetric circumferential skin creases (CSCSC). To date, six cases of CSCSC and eight cases of CDCBM caused by nine heterozygous variants have been reported. Here we report two cases with novel de novo missense TUBB variants (NM_178014.4:c.863A>G, p.(Glu288Gly) and c.869C>T, p.(Thr290Ile)). Case 1 presented brain malformations consistent with tubulinopathies including abnormalities in cortex, basal ganglia, corpus callosum, brain stem, and cerebellum along with other systemic features such as coloboma, facial dysmorphisms, vesicoureteral reflux, hypoplastic kidney, and cutis laxa-like mild skin loosening. Another case presented abnormalities of the corpus callosum, brain stem, and cerebellum along with facial dysmorphisms. We reviewed previous literature and suggest the diversity of clinical findings of TUBB-related disorders.

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References

1. Breuss M, Keays DA. Microtubules and neurodevelopmental disease: the movers and the makers. Adv Exp Med Biol. 2014;800:75–96. - DOI
1. Romaniello R, Arrigoni F, Fry AE, Bassi MT, Rees MI, Borgatti R, et al. Tubulin genes and malformations of cortical development. Eur J Med Genet. 2018;61:744–54. - DOI
1. Breuss M, Heng JI, Poirier K, Tian G, Jaglin XH, Qu Z, et al. Mutations in the β-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities. Cell Rep. 2012;2:1554–62. - DOI
1. Isrie M, Breuss M, Tian G, Hansen AH, Cristofoli F, Morandell J, et al. Mutations in either TUBB or MAPRE2 cause circumferential skin creases kunze type. Am J Hum Genet. 2015;97:790–800. - DOI
1. Tadaka S, Hishinuma E, Komaki S, Motoike IN, Kawashima J, Saigusa D, et al. jMorp updates in 2020: large enhancement of multi-omics data resources on the general Japanese population. Nucleic Acids Res. 2021;49:D536–D544. - DOI

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[1] Breuss M, Keays DA. Microtubules and neurodevelopmental disease: the movers and the makers. Adv Exp Med Biol. 2014;800:75–96. - DOI

[2] Breuss M, Keays DA. Microtubules and neurodevelopmental disease: the movers and the makers. Adv Exp Med Biol. 2014;800:75–96. - DOI

[3] Romaniello R, Arrigoni F, Fry AE, Bassi MT, Rees MI, Borgatti R, et al. Tubulin genes and malformations of cortical development. Eur J Med Genet. 2018;61:744–54. - DOI

[4] Romaniello R, Arrigoni F, Fry AE, Bassi MT, Rees MI, Borgatti R, et al. Tubulin genes and malformations of cortical development. Eur J Med Genet. 2018;61:744–54. - DOI

[5] Breuss M, Heng JI, Poirier K, Tian G, Jaglin XH, Qu Z, et al. Mutations in the β-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities. Cell Rep. 2012;2:1554–62. - DOI

[6] Breuss M, Heng JI, Poirier K, Tian G, Jaglin XH, Qu Z, et al. Mutations in the β-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities. Cell Rep. 2012;2:1554–62. - DOI

[7] Isrie M, Breuss M, Tian G, Hansen AH, Cristofoli F, Morandell J, et al. Mutations in either TUBB or MAPRE2 cause circumferential skin creases kunze type. Am J Hum Genet. 2015;97:790–800. - DOI

[8] Isrie M, Breuss M, Tian G, Hansen AH, Cristofoli F, Morandell J, et al. Mutations in either TUBB or MAPRE2 cause circumferential skin creases kunze type. Am J Hum Genet. 2015;97:790–800. - DOI

[9] Tadaka S, Hishinuma E, Komaki S, Motoike IN, Kawashima J, Saigusa D, et al. jMorp updates in 2020: large enhancement of multi-omics data resources on the general Japanese population. Nucleic Acids Res. 2021;49:D536–D544. - DOI

[10] Tadaka S, Hishinuma E, Komaki S, Motoike IN, Kawashima J, Saigusa D, et al. jMorp updates in 2020: large enhancement of multi-omics data resources on the general Japanese population. Nucleic Acids Res. 2021;49:D536–D544. - DOI

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Identification of two novel de novo TUBB variants in cases with brain malformations: case reports and literature review

Affiliations

Identification of two novel de novo TUBB variants in cases with brain malformations: case reports and literature review

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