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CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures

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CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures. / Sargolzaeiaval, Forough; Zhang, Jiaming; Schleit, Jennifer; Lessel, Davor; Kubisch, Christian; Precioso, Debora R; Sillence, David; Hisama, Fuki M; Dorschner, Michael; Martin, George M; Oshima, Junko.

In: MOL GENET GENOM MED, Vol. 6, No. 6, 11.2018, p. 1148-1156.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sargolzaeiaval, F, Zhang, J, Schleit, J, Lessel, D, Kubisch, C, Precioso, DR, Sillence, D, Hisama, FM, Dorschner, M, Martin, GM & Oshima, J 2018, 'CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures', MOL GENET GENOM MED, vol. 6, no. 6, pp. 1148-1156. https://doi.org/10.1002/mgg3.495

APA

Sargolzaeiaval, F., Zhang, J., Schleit, J., Lessel, D., Kubisch, C., Precioso, D. R., Sillence, D., Hisama, F. M., Dorschner, M., Martin, G. M., & Oshima, J. (2018). CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures. MOL GENET GENOM MED, 6(6), 1148-1156. https://doi.org/10.1002/mgg3.495

Vancouver

Sargolzaeiaval F, Zhang J, Schleit J, Lessel D, Kubisch C, Precioso DR et al. CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures. MOL GENET GENOM MED. 2018 Nov;6(6):1148-1156. https://doi.org/10.1002/mgg3.495

Bibtex

@article{d9d28de63b28423093b326c50aca7d11,
title = "CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures",
abstract = "BACKGROUND: Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is an autosomal recessive disorder caused by pathogenic variants of the conserved telomere maintenance component 1 (CTC1) gene. The CTC1 forms the telomeric capping complex, CST, which functions in telomere homeostasis and replication.METHODS: A Brazilian pedigree and an Australian pedigree were referred to the International Registry of Werner Syndrome (Seattle, WA, USA), with clinical features of accelerated aging and recurrent bone fractures. Whole exome sequencing was performed to identify the genetic causes.RESULTS: Whole exome sequencing of the Brazilian pedigree revealed compound heterozygous pathogenic variants in CTC1: a missense mutation (c.2959C>T, p.Arg987Trp) and a novel stop codon change (c.322C>T, p.Arg108*). The Australian patient carried two novel heterozygous CTC1 variants, c.2916G>T, p.Val972Gly and c.2926G>T, p.Val976Phe within the same allele. Both heterozygous variants were inherited from the unaffected father, excluding the diagnosis of CRMCC in this pedigree. Cell biological studies demonstrated accumulation of double strand break foci in lymphoblastoid cell lines derived from the patients. Increased DSB foci were extended to non-telomeric regions of the genome, in agreement with previous biochemical studies showing a preferential binding of CTC1 protein to GC-rich sequences.CONCLUSION: CTC1 pathogenic variants can present with unusual manifestations of progeria accompanied with recurrent bone fractures. Further studies are needed to elucidate the disease mechanism leading to the clinical presentation with intra-familial variations of CRMCC.",
keywords = "Journal Article",
author = "Forough Sargolzaeiaval and Jiaming Zhang and Jennifer Schleit and Davor Lessel and Christian Kubisch and Precioso, {Debora R} and David Sillence and Hisama, {Fuki M} and Michael Dorschner and Martin, {George M} and Junko Oshima",
note = "{\textcopyright} 2018 University of Washington. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.",
year = "2018",
month = nov,
doi = "10.1002/mgg3.495",
language = "English",
volume = "6",
pages = "1148--1156",
journal = "MOL GENET GENOM MED",
issn = "2324-9269",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

RIS

TY - JOUR

T1 - CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures

AU - Sargolzaeiaval, Forough

AU - Zhang, Jiaming

AU - Schleit, Jennifer

AU - Lessel, Davor

AU - Kubisch, Christian

AU - Precioso, Debora R

AU - Sillence, David

AU - Hisama, Fuki M

AU - Dorschner, Michael

AU - Martin, George M

AU - Oshima, Junko

N1 - © 2018 University of Washington. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

PY - 2018/11

Y1 - 2018/11

N2 - BACKGROUND: Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is an autosomal recessive disorder caused by pathogenic variants of the conserved telomere maintenance component 1 (CTC1) gene. The CTC1 forms the telomeric capping complex, CST, which functions in telomere homeostasis and replication.METHODS: A Brazilian pedigree and an Australian pedigree were referred to the International Registry of Werner Syndrome (Seattle, WA, USA), with clinical features of accelerated aging and recurrent bone fractures. Whole exome sequencing was performed to identify the genetic causes.RESULTS: Whole exome sequencing of the Brazilian pedigree revealed compound heterozygous pathogenic variants in CTC1: a missense mutation (c.2959C>T, p.Arg987Trp) and a novel stop codon change (c.322C>T, p.Arg108*). The Australian patient carried two novel heterozygous CTC1 variants, c.2916G>T, p.Val972Gly and c.2926G>T, p.Val976Phe within the same allele. Both heterozygous variants were inherited from the unaffected father, excluding the diagnosis of CRMCC in this pedigree. Cell biological studies demonstrated accumulation of double strand break foci in lymphoblastoid cell lines derived from the patients. Increased DSB foci were extended to non-telomeric regions of the genome, in agreement with previous biochemical studies showing a preferential binding of CTC1 protein to GC-rich sequences.CONCLUSION: CTC1 pathogenic variants can present with unusual manifestations of progeria accompanied with recurrent bone fractures. Further studies are needed to elucidate the disease mechanism leading to the clinical presentation with intra-familial variations of CRMCC.

AB - BACKGROUND: Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is an autosomal recessive disorder caused by pathogenic variants of the conserved telomere maintenance component 1 (CTC1) gene. The CTC1 forms the telomeric capping complex, CST, which functions in telomere homeostasis and replication.METHODS: A Brazilian pedigree and an Australian pedigree were referred to the International Registry of Werner Syndrome (Seattle, WA, USA), with clinical features of accelerated aging and recurrent bone fractures. Whole exome sequencing was performed to identify the genetic causes.RESULTS: Whole exome sequencing of the Brazilian pedigree revealed compound heterozygous pathogenic variants in CTC1: a missense mutation (c.2959C>T, p.Arg987Trp) and a novel stop codon change (c.322C>T, p.Arg108*). The Australian patient carried two novel heterozygous CTC1 variants, c.2916G>T, p.Val972Gly and c.2926G>T, p.Val976Phe within the same allele. Both heterozygous variants were inherited from the unaffected father, excluding the diagnosis of CRMCC in this pedigree. Cell biological studies demonstrated accumulation of double strand break foci in lymphoblastoid cell lines derived from the patients. Increased DSB foci were extended to non-telomeric regions of the genome, in agreement with previous biochemical studies showing a preferential binding of CTC1 protein to GC-rich sequences.CONCLUSION: CTC1 pathogenic variants can present with unusual manifestations of progeria accompanied with recurrent bone fractures. Further studies are needed to elucidate the disease mechanism leading to the clinical presentation with intra-familial variations of CRMCC.

KW - Journal Article

U2 - 10.1002/mgg3.495

DO - 10.1002/mgg3.495

M3 - SCORING: Journal article

C2 - 30393977

VL - 6

SP - 1148

EP - 1156

JO - MOL GENET GENOM MED

JF - MOL GENET GENOM MED

SN - 2324-9269

IS - 6

ER -