Diagnosis of TBC1D32-associated conditions: Expanding the phenotypic spectrum of a complex ciliopathy

Sarah C. Harris; Karen Chong; David Chitayat; Kelly L. Gilmore; Alexander A.L. Jorge; Bruna L. Freire; Antonio Lerario; Patrick Shannon; Heidi Cope; William B. Gallentine; Gwenal Le Guyader; Frederic Bilan; Pascaline Létard; Erica E. Davis; Neeta L. Vora

doi:10.1002/ajmg.a.63150

Diagnosis of TBC1D32-associated conditions: Expanding the phenotypic spectrum of a complex ciliopathy

Sarah C. Harris^*, Karen Chong, David Chitayat, Kelly L. Gilmore, Alexander A.L. Jorge, Bruna L. Freire, Antonio Lerario, Patrick Shannon, Heidi Cope, William B. Gallentine, Gwenal Le Guyader, Frederic Bilan, Pascaline Létard, Erica E. Davis, Neeta L. Vora

^*Corresponding author for this work

Pediatrics

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

2 Scopus citations

Abstract

Exome sequencing is a powerful tool in prenatal and postnatal genetics and can help identify novel candidate genes critical to human development. We describe seven unpublished probands with rare likely pathogenic variants or variants of uncertain significance that segregate with recessive disease in TBC1D32, including four fetal probands in three unrelated pedigrees and three pediatric probands in unrelated pedigrees. We also report clinical comparisons with seven previously published patients. Index probands were identified through an ongoing prenatal exome sequencing study and through an online data sharing platform (Gene Matcher™). A literature review was also completed. TBC1D32 is involved in the development and function of cilia and is expressed in the developing hypothalamus and pituitary gland. We provide additional data to expand the phenotype correlated with TBC1D32 variants, including a severe prenatal phenotype associated with life-limiting congenital anomalies.

Original language	English (US)
Pages (from-to)	1282-1292
Number of pages	11
Journal	American Journal of Medical Genetics, Part A
Volume	191
Issue number	5
DOIs	https://doi.org/10.1002/ajmg.a.63150
State	Published - May 2023

Funding

This work was funded by US National Institutes of Health grants R21TR002770 (Neeta L. Vora and Erica E. Davis), R01HD105868 (Neeta L. Vora and Erica E. Davis), R01DK072301 (Erica E. Davis), and R01HD042601 (Erica E. Davis). Sao Paulo Research Foundation—FAPESP (grants 2013/03236‐5 to Alexander A. L. Jorge and 2018/10893‐6 to Bruna L. Freire); and the National Council for Scientific and Technological Development—CNPq (grant 303294/2020‐5 to Alexander A. L. Jorge). Erica E. Davis is the Ann Marie and Francis Klocke, MD research scholar. Conselho Nacional de Desenvolvimento Científico e Tecnológico; US National Institutes of Health, Grant/Award Numbers: R01HD042601, R01DK072301, R01HD105868, R21TR002770; Sao Paulo Research Foundation, Grant/Award Numbers: 2018/10893‐6, 2013/03236‐5; the National Council for Scientific and Technological Development, Grant/Award Number: 303294/2020‐5 Funding information US National Institutes of Health grants R21TR002770 (Neeta L. Vora and Erica E. Davis), R01HD105868 (Neeta L. Vora and Erica E. Davis), R01DK072301 (Erica E. Davis), and R01HD042601 (Erica E. Davis). Sao Paulo Research Foundation—FAPESP (grants 2013/03236‐5 to Alexander A. L. Jorge and 2018/10893‐6 to Bruna L. Freire) and the National Council for Scientific and Technological Development—CNPq (grant 303294/2020‐5 to Alexander A. L. Jorge). Erica E. Davis is the Ann Marie and Francis Klocke, MD research scholar.

Keywords

TBC1D32
ciliopathy
exome sequencing
prenatal phenotype

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1002/ajmg.a.63150

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Harris, S. C., Chong, K., Chitayat, D., Gilmore, K. L., Jorge, A. A. L., Freire, B. L., Lerario, A., Shannon, P., Cope, H., Gallentine, W. B., Le Guyader, G., Bilan, F., Létard, P., Davis, E. E., & Vora, N. L. (2023). Diagnosis of TBC1D32-associated conditions: Expanding the phenotypic spectrum of a complex ciliopathy. American Journal of Medical Genetics, Part A, 191(5), 1282-1292. https://doi.org/10.1002/ajmg.a.63150

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abstract = "Exome sequencing is a powerful tool in prenatal and postnatal genetics and can help identify novel candidate genes critical to human development. We describe seven unpublished probands with rare likely pathogenic variants or variants of uncertain significance that segregate with recessive disease in TBC1D32, including four fetal probands in three unrelated pedigrees and three pediatric probands in unrelated pedigrees. We also report clinical comparisons with seven previously published patients. Index probands were identified through an ongoing prenatal exome sequencing study and through an online data sharing platform (Gene Matcher{\texttrademark}). A literature review was also completed. TBC1D32 is involved in the development and function of cilia and is expressed in the developing hypothalamus and pituitary gland. We provide additional data to expand the phenotype correlated with TBC1D32 variants, including a severe prenatal phenotype associated with life-limiting congenital anomalies.",

keywords = "TBC1D32, ciliopathy, exome sequencing, prenatal phenotype",

author = "Harris, {Sarah C.} and Karen Chong and David Chitayat and Gilmore, {Kelly L.} and Jorge, {Alexander A.L.} and Freire, {Bruna L.} and Antonio Lerario and Patrick Shannon and Heidi Cope and Gallentine, {William B.} and {Le Guyader}, Gwenal and Frederic Bilan and Pascaline L{\'e}tard and Davis, {Erica E.} and Vora, {Neeta L.}",

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Harris, SC, Chong, K, Chitayat, D, Gilmore, KL, Jorge, AAL, Freire, BL, Lerario, A, Shannon, P, Cope, H, Gallentine, WB, Le Guyader, G, Bilan, F, Létard, P, Davis, EE & Vora, NL 2023, 'Diagnosis of TBC1D32-associated conditions: Expanding the phenotypic spectrum of a complex ciliopathy', American Journal of Medical Genetics, Part A, vol. 191, no. 5, pp. 1282-1292. https://doi.org/10.1002/ajmg.a.63150

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AU - Harris, Sarah C.

AU - Chong, Karen

AU - Chitayat, David

AU - Gilmore, Kelly L.

AU - Jorge, Alexander A.L.

AU - Freire, Bruna L.

AU - Lerario, Antonio

AU - Shannon, Patrick

AU - Cope, Heidi

AU - Gallentine, William B.

AU - Le Guyader, Gwenal

AU - Bilan, Frederic

AU - Létard, Pascaline

AU - Davis, Erica E.

AU - Vora, Neeta L.

PY - 2023/5

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AB - Exome sequencing is a powerful tool in prenatal and postnatal genetics and can help identify novel candidate genes critical to human development. We describe seven unpublished probands with rare likely pathogenic variants or variants of uncertain significance that segregate with recessive disease in TBC1D32, including four fetal probands in three unrelated pedigrees and three pediatric probands in unrelated pedigrees. We also report clinical comparisons with seven previously published patients. Index probands were identified through an ongoing prenatal exome sequencing study and through an online data sharing platform (Gene Matcher™). A literature review was also completed. TBC1D32 is involved in the development and function of cilia and is expressed in the developing hypothalamus and pituitary gland. We provide additional data to expand the phenotype correlated with TBC1D32 variants, including a severe prenatal phenotype associated with life-limiting congenital anomalies.

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Diagnosis of TBC1D32-associated conditions: Expanding the phenotypic spectrum of a complex ciliopathy

Abstract

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Keywords

ASJC Scopus subject areas

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