Two New Cases Expand the Phenotypic Spectrum of TUBG1 Missense Variants

Roser Urreizti; Jessica Vissicchio; Mohamed Idries; Monica Cozar; Raquel Rabionet; Tyhiesia Donald; Elizabeth J. Bhoj; Tomoki T. Nomakuchi; Shannon C. Shipley; Andrew E. Timms; Ghayda M. Mirzaa; Mercedes Serrano; Andrew K. Sobering

doi:10.1002/ajmg.a.64095

Two New Cases Expand the Phenotypic Spectrum of TUBG1 Missense Variants

Roser Urreizti, Jessica Vissicchio, Mohamed Idries, Monica Cozar, Raquel Rabionet, Tyhiesia Donald, Elizabeth J. Bhoj, Tomoki T. Nomakuchi, Shannon C. Shipley, Andrew E. Timms, Ghayda M. Mirzaa, Mercedes Serrano, Andrew K. Sobering

Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

Abstract

The gamma-tubulin ring complex (γ-TuRC) plays a role in coordinating centrosome and spindle pole body formation during cell division. TUBG1 encodes a critical component of the γ-TuRC. Pathogenic TUBG1 variants can cause a range of alterations in cortical gyral patterning, microcephaly, and other neurological manifestations. We describe two missense variants in TUBG1 and their associated clinical phenotypes. One individual has microcephaly, epilepsy, and a simplified gyral pattern with a TUBG1 variant interpreted as pathogenic. The other individual has a likely pathogenic TUBG1 variant that explains the milder presentation of autism spectrum disorder, intellectual disability, later-onset well-controlled epilepsy, a normocephalic head size, and no detectable structural abnormalities on neuroimaging.

Original language	English (US)
Journal	American Journal of Medical Genetics, Part A
DOIs	https://doi.org/10.1002/ajmg.a.64095
State	Accepted/In press - 2025

Keywords

epilepsy
intellectual disability
lissencephaly
microcephaly
TUBG1

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1002/ajmg.a.64095

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title = "Two New Cases Expand the Phenotypic Spectrum of TUBG1 Missense Variants",

abstract = "The gamma-tubulin ring complex (γ-TuRC) plays a role in coordinating centrosome and spindle pole body formation during cell division. TUBG1 encodes a critical component of the γ-TuRC. Pathogenic TUBG1 variants can cause a range of alterations in cortical gyral patterning, microcephaly, and other neurological manifestations. We describe two missense variants in TUBG1 and their associated clinical phenotypes. One individual has microcephaly, epilepsy, and a simplified gyral pattern with a TUBG1 variant interpreted as pathogenic. The other individual has a likely pathogenic TUBG1 variant that explains the milder presentation of autism spectrum disorder, intellectual disability, later-onset well-controlled epilepsy, a normocephalic head size, and no detectable structural abnormalities on neuroimaging.",

keywords = "epilepsy, intellectual disability, lissencephaly, microcephaly, TUBG1",

author = "Roser Urreizti and Jessica Vissicchio and Mohamed Idries and Monica Cozar and Raquel Rabionet and Tyhiesia Donald and Bhoj, {Elizabeth J.} and Nomakuchi, {Tomoki T.} and Shipley, {Shannon C.} and Timms, {Andrew E.} and Mirzaa, {Ghayda M.} and Mercedes Serrano and Sobering, {Andrew K.}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.",

year = "2025",

doi = "10.1002/ajmg.a.64095",

language = "English (US)",

journal = "American Journal of Medical Genetics, Part A",

issn = "1552-4825",

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AU - Urreizti, Roser

AU - Vissicchio, Jessica

AU - Idries, Mohamed

AU - Cozar, Monica

AU - Rabionet, Raquel

AU - Donald, Tyhiesia

AU - Bhoj, Elizabeth J.

AU - Nomakuchi, Tomoki T.

AU - Shipley, Shannon C.

AU - Timms, Andrew E.

AU - Mirzaa, Ghayda M.

AU - Serrano, Mercedes

AU - Sobering, Andrew K.

PY - 2025

Y1 - 2025

N2 - The gamma-tubulin ring complex (γ-TuRC) plays a role in coordinating centrosome and spindle pole body formation during cell division. TUBG1 encodes a critical component of the γ-TuRC. Pathogenic TUBG1 variants can cause a range of alterations in cortical gyral patterning, microcephaly, and other neurological manifestations. We describe two missense variants in TUBG1 and their associated clinical phenotypes. One individual has microcephaly, epilepsy, and a simplified gyral pattern with a TUBG1 variant interpreted as pathogenic. The other individual has a likely pathogenic TUBG1 variant that explains the milder presentation of autism spectrum disorder, intellectual disability, later-onset well-controlled epilepsy, a normocephalic head size, and no detectable structural abnormalities on neuroimaging.

AB - The gamma-tubulin ring complex (γ-TuRC) plays a role in coordinating centrosome and spindle pole body formation during cell division. TUBG1 encodes a critical component of the γ-TuRC. Pathogenic TUBG1 variants can cause a range of alterations in cortical gyral patterning, microcephaly, and other neurological manifestations. We describe two missense variants in TUBG1 and their associated clinical phenotypes. One individual has microcephaly, epilepsy, and a simplified gyral pattern with a TUBG1 variant interpreted as pathogenic. The other individual has a likely pathogenic TUBG1 variant that explains the milder presentation of autism spectrum disorder, intellectual disability, later-onset well-controlled epilepsy, a normocephalic head size, and no detectable structural abnormalities on neuroimaging.

KW - epilepsy

KW - intellectual disability

KW - lissencephaly

KW - microcephaly

KW - TUBG1

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DO - 10.1002/ajmg.a.64095

M3 - Article

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SN - 1552-4825

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

ER -

Two New Cases Expand the Phenotypic Spectrum of TUBG1 Missense Variants

Abstract

Keywords

ASJC Scopus subject areas

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