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Biallelic pathogenic variants in TBCD-related neurodevelopment disease with mild clinical features

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Abstract

Background

Microtubule dynamics is crucial for neuronal function and survival. The disrupted function of microtubule dynamics would lead to neurodegenerative and neurodevelopmental disorders. Tubulin-specific chaperone D (TBCD) is one of five tubulin co-chaperones acted in assembly and disassembly dynamics of microtubule. The biallelic pathogenic variants of TBCD gene were reported to be associated with severe degenerative encephalopathy accompanied with seizures previously.

Results

Compound heterozygous variants were identified in three patients from three families. The in silico prediction software and ACMG standards and guidelines proved the pathogenicity of the TBCD pathogenic variants. The clinical features of the three patients presented with mild neurodevelopmental manifestations including autism spectrum disorder (ASD) and occasional generalized tonic-clonic seizures (GTCSs) responding well to antiepileptic drugs.

Conclusion

Our research expanded the clinical spectrum of TBCD-related neurodevelopmental disease which contributed to understanding the genotype-phenotype correlations of the disease.

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Abbreviations

ASD:

autism spectrum disorder

GTCS:

generalized tonic-clonic seizures

TBCD:

tubulin-specific chaperone D

EEG:

electroencephalogram

MRI:

magnetic resonance imaging

DSM:

American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders

WES:

whole-exome sequencing

SIFT:

Sorting Intolerant from Tolerant

PolyPhen-2:

Polymorphism Phenotyping v2

CADD:

Combined Annotation–Dependent Depletion

ACMG:

the international guidelines of the American College of Medical Genetics

MAPs:

microtubule-interacting proteins

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Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81801136) and China Postdoctoral Science Foundation.

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Authors and Affiliations

  1. Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008, Hunan, China

    Di Tian & Khan Rizwan

  2. Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China

    Yi Liu, Lulu Kang & Yanlin Yang

  3. Department of Medical Genetics, Maternal and Child Health Hospital of Hunan province, Changsha, 410008, China

    Xiao Mao & Li Shu

Authors
  1. Di Tian
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  2. Khan Rizwan
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  3. Yi Liu
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  4. Lulu Kang
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  5. Yanlin Yang
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  6. Xiao Mao
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  7. Li Shu
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Corresponding authors

Correspondence to Xiao Mao or Li Shu.

Ethics declarations

Ethics approval and consent to participate

The parents included in our research all had informed consents, and the study was approved by the Ethics Committee of Xiangya Hospital.

Consent for publication

We have obtained consent to publish from the participants’ parents to report individual patient data.

Availability of data and material

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

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The authors declare that they have no competing interests.

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Electronic supplementary material

Supplementary Figure 1

MRI of patient 1 which revealed hypointensities in T1-weighted image and hyperintensities in T2-weighted image in white matter in occipital lobe. (PNG 259 kb)

High resolution image (TIF 191 kb)

Supplementary Figure 2

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High resolution image (TIF 222 kb)

Supplementary Figure 3

MRI of patient 2 which revealed hypointensities in T1-weighted image and hyperintensities in T2-weighted image in white matter in occipital lobe. (PNG 269 kb)

High resolution image (TIF 194 kb)

Supplementary Figure 4

(PNG 341 kb)

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Supplementary Figure 5

MRI of patient 3. (PNG 699 kb)

High resolution image (TIF 242 kb)

Supplementary Figure 6

(PNG 768 kb)

High resolution image (TIF 243 kb)

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Cite this article

Tian, D., Rizwan, K., Liu, Y. et al. Biallelic pathogenic variants in TBCD-related neurodevelopment disease with mild clinical features. Neurol Sci 40, 2325–2331 (2019). https://doi.org/10.1007/s10072-019-03979-0

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  • DOI: https://doi.org/10.1007/s10072-019-03979-0

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