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Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities

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Harvard

Quintana, AM, Yu, H-C, Brebner, A, Pupavac, M, Geiger, EA, Watson, A, Castro, VL, Cheung, W, Chen, S-H, Watkins, D, Pastinen, T, Skovby, F, Appel, B, Rosenblatt, DS & Shaikh, TH 2017, 'Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities' Human Molecular Genetics, bind 26, nr. 15, s. 2838-2849. https://doi.org/10.1093/hmg/ddx157

APA

Quintana, A. M., Yu, H-C., Brebner, A., Pupavac, M., Geiger, E. A., Watson, A., ... Shaikh, T. H. (2017). Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities. Human Molecular Genetics, 26(15), 2838-2849. https://doi.org/10.1093/hmg/ddx157

CBE

Quintana AM, Yu H-C, Brebner A, Pupavac M, Geiger EA, Watson A, Castro VL, Cheung W, Chen S-H, Watkins D, Pastinen T, Skovby F, Appel B, Rosenblatt DS, Shaikh TH. 2017. Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities. Human Molecular Genetics. 26(15):2838-2849. https://doi.org/10.1093/hmg/ddx157

MLA

Vancouver

Author

Quintana, Anita M ; Yu, Hung-Chun ; Brebner, Alison ; Pupavac, Mihaela ; Geiger, Elizabeth A ; Watson, Abigail ; Castro, Victoria L ; Cheung, Warren ; Chen, Shu-Huang ; Watkins, David ; Pastinen, Tomi ; Skovby, Flemming ; Appel, Bruce ; Rosenblatt, David S ; Shaikh, Tamim H. / Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities. I: Human Molecular Genetics. 2017 ; Bind 26, Nr. 15. s. 2838-2849.

Bibtex

@article{7c4552a8193c41d6a30ed83d24e79662,
title = "Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities",
abstract = "CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutation of THAP11 also results in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with clinical and biochemical phenotypic features that overlap cblX, but who does not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant, c.240C > G (p.Phe80Leu). Functional analysis in the developing zebrafish embryo demonstrated that both THAP11 and HCFC1 regulate the proliferation and differentiation of neural precursors, suggesting important roles in normal brain development. The loss of THAP11 in zebrafish embryos results in craniofacial abnormalities including the complete loss of Meckel's cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work that demonstrated a role for HCFC1 in vertebrate craniofacial development. High throughput RNA-sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11. Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin metabolism as well as other pathways involved in early vertebrate development.",
keywords = "Animals, Base Sequence, Branchial Region, Cell Differentiation, Child, Craniofacial Abnormalities, Fibroblasts, Gene Expression Regulation, Host Cell Factor C1, Humans, Mutation, Primary Cell Culture, Repressor Proteins, Transcription, Genetic, Vitamin B 12, Zebrafish, Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural",
author = "Quintana, {Anita M} and Hung-Chun Yu and Alison Brebner and Mihaela Pupavac and Geiger, {Elizabeth A} and Abigail Watson and Castro, {Victoria L} and Warren Cheung and Shu-Huang Chen and David Watkins and Tomi Pastinen and Flemming Skovby and Bruce Appel and Rosenblatt, {David S} and Shaikh, {Tamim H}",
note = "{\circledC} The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.",
year = "2017",
month = "8",
day = "1",
doi = "10.1093/hmg/ddx157",
language = "English",
volume = "26",
pages = "2838--2849",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "15",

}

RIS

TY - JOUR

T1 - Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities

AU - Quintana, Anita M

AU - Yu, Hung-Chun

AU - Brebner, Alison

AU - Pupavac, Mihaela

AU - Geiger, Elizabeth A

AU - Watson, Abigail

AU - Castro, Victoria L

AU - Cheung, Warren

AU - Chen, Shu-Huang

AU - Watkins, David

AU - Pastinen, Tomi

AU - Skovby, Flemming

AU - Appel, Bruce

AU - Rosenblatt, David S

AU - Shaikh, Tamim H

N1 - © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutation of THAP11 also results in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with clinical and biochemical phenotypic features that overlap cblX, but who does not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant, c.240C > G (p.Phe80Leu). Functional analysis in the developing zebrafish embryo demonstrated that both THAP11 and HCFC1 regulate the proliferation and differentiation of neural precursors, suggesting important roles in normal brain development. The loss of THAP11 in zebrafish embryos results in craniofacial abnormalities including the complete loss of Meckel's cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work that demonstrated a role for HCFC1 in vertebrate craniofacial development. High throughput RNA-sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11. Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin metabolism as well as other pathways involved in early vertebrate development.

AB - CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutation of THAP11 also results in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with clinical and biochemical phenotypic features that overlap cblX, but who does not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant, c.240C > G (p.Phe80Leu). Functional analysis in the developing zebrafish embryo demonstrated that both THAP11 and HCFC1 regulate the proliferation and differentiation of neural precursors, suggesting important roles in normal brain development. The loss of THAP11 in zebrafish embryos results in craniofacial abnormalities including the complete loss of Meckel's cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work that demonstrated a role for HCFC1 in vertebrate craniofacial development. High throughput RNA-sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11. Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin metabolism as well as other pathways involved in early vertebrate development.

KW - Animals

KW - Base Sequence

KW - Branchial Region

KW - Cell Differentiation

KW - Child

KW - Craniofacial Abnormalities

KW - Fibroblasts

KW - Gene Expression Regulation

KW - Host Cell Factor C1

KW - Humans

KW - Mutation

KW - Primary Cell Culture

KW - Repressor Proteins

KW - Transcription, Genetic

KW - Vitamin B 12

KW - Zebrafish

KW - Case Reports

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, N.I.H., Extramural

U2 - 10.1093/hmg/ddx157

DO - 10.1093/hmg/ddx157

M3 - Journal article

VL - 26

SP - 2838

EP - 2849

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 15

ER -

ID: 52804175