Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency

Brody Holohan, Wanil Kim, Tsung Po Lai, Hirotoshi Hoshiyama, Ning Zhang, Anas M. Alazami, Woodring E. Wright, M. Stephen Meyn, Fowzan S. Alkuraya, Jerry W. Shay

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Loss of function in genes required for telomere maintenance result in disorders known as telomeropathies, which are characterized by a pattern of symptoms including generalized and specific lymphocytopenias as well as very short telomere length and disease anticipation. Methods: Because human LARP7 is the most likely ortholog of the Tetrahymena p65 protein, which is required for telomerase activity in that organism, we investigated the effects of LARP7 silencing in human cells as well as in two distinct families with Alazami syndrome (loss of function of LARP7). Results: Depletion of LARP7 caused a reduction in telomerase enzymatic activity and progressively shorter telomeres in human cancer cell lines. Alazami syndrome patients from two separate cohorts exhibited very short lymphocyte telomeres. Further, wild-type offspring of LARP7 mutant individuals also had very short telomeres, comparable to what is observed in telomerase (hTERT) mutant cohorts. Conclusions: Together, these experiments demonstrate that in addition to the readily apparent developmental disorder associated with LARP7 deficiency, an underlying telomeropathy exists even in unaffected siblings of these individuals.

Original languageEnglish (US)
Article number749
JournalBMC Genomics
Volume17
DOIs
StatePublished - Oct 17 2016

Fingerprint

Telomere
Maintenance
Telomerase
Lymphopenia
Siblings
Lymphocytes
Cell Line
Genes
Neoplasms

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency. / Holohan, Brody; Kim, Wanil; Lai, Tsung Po; Hoshiyama, Hirotoshi; Zhang, Ning; Alazami, Anas M.; Wright, Woodring E.; Meyn, M. Stephen; Alkuraya, Fowzan S.; Shay, Jerry W.

In: BMC Genomics, Vol. 17, 749, 17.10.2016.

Research output: Contribution to journalArticle

Holohan, B, Kim, W, Lai, TP, Hoshiyama, H, Zhang, N, Alazami, AM, Wright, WE, Meyn, MS, Alkuraya, FS & Shay, JW 2016, 'Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency', BMC Genomics, vol. 17, 749. https://doi.org/10.1186/s12864-016-3093-4
Holohan B, Kim W, Lai TP, Hoshiyama H, Zhang N, Alazami AM et al. Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency. BMC Genomics. 2016 Oct 17;17. 749. https://doi.org/10.1186/s12864-016-3093-4
Holohan, Brody ; Kim, Wanil ; Lai, Tsung Po ; Hoshiyama, Hirotoshi ; Zhang, Ning ; Alazami, Anas M. ; Wright, Woodring E. ; Meyn, M. Stephen ; Alkuraya, Fowzan S. ; Shay, Jerry W. / Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency. In: BMC Genomics. 2016 ; Vol. 17.
@article{48669ff04898443eb547f9ca18498b92,
title = "Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency",
abstract = "Background: Loss of function in genes required for telomere maintenance result in disorders known as telomeropathies, which are characterized by a pattern of symptoms including generalized and specific lymphocytopenias as well as very short telomere length and disease anticipation. Methods: Because human LARP7 is the most likely ortholog of the Tetrahymena p65 protein, which is required for telomerase activity in that organism, we investigated the effects of LARP7 silencing in human cells as well as in two distinct families with Alazami syndrome (loss of function of LARP7). Results: Depletion of LARP7 caused a reduction in telomerase enzymatic activity and progressively shorter telomeres in human cancer cell lines. Alazami syndrome patients from two separate cohorts exhibited very short lymphocyte telomeres. Further, wild-type offspring of LARP7 mutant individuals also had very short telomeres, comparable to what is observed in telomerase (hTERT) mutant cohorts. Conclusions: Together, these experiments demonstrate that in addition to the readily apparent developmental disorder associated with LARP7 deficiency, an underlying telomeropathy exists even in unaffected siblings of these individuals.",
author = "Brody Holohan and Wanil Kim and Lai, {Tsung Po} and Hirotoshi Hoshiyama and Ning Zhang and Alazami, {Anas M.} and Wright, {Woodring E.} and Meyn, {M. Stephen} and Alkuraya, {Fowzan S.} and Shay, {Jerry W.}",
year = "2016",
month = "10",
day = "17",
doi = "10.1186/s12864-016-3093-4",
language = "English (US)",
volume = "17",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency

AU - Holohan, Brody

AU - Kim, Wanil

AU - Lai, Tsung Po

AU - Hoshiyama, Hirotoshi

AU - Zhang, Ning

AU - Alazami, Anas M.

AU - Wright, Woodring E.

AU - Meyn, M. Stephen

AU - Alkuraya, Fowzan S.

AU - Shay, Jerry W.

PY - 2016/10/17

Y1 - 2016/10/17

N2 - Background: Loss of function in genes required for telomere maintenance result in disorders known as telomeropathies, which are characterized by a pattern of symptoms including generalized and specific lymphocytopenias as well as very short telomere length and disease anticipation. Methods: Because human LARP7 is the most likely ortholog of the Tetrahymena p65 protein, which is required for telomerase activity in that organism, we investigated the effects of LARP7 silencing in human cells as well as in two distinct families with Alazami syndrome (loss of function of LARP7). Results: Depletion of LARP7 caused a reduction in telomerase enzymatic activity and progressively shorter telomeres in human cancer cell lines. Alazami syndrome patients from two separate cohorts exhibited very short lymphocyte telomeres. Further, wild-type offspring of LARP7 mutant individuals also had very short telomeres, comparable to what is observed in telomerase (hTERT) mutant cohorts. Conclusions: Together, these experiments demonstrate that in addition to the readily apparent developmental disorder associated with LARP7 deficiency, an underlying telomeropathy exists even in unaffected siblings of these individuals.

AB - Background: Loss of function in genes required for telomere maintenance result in disorders known as telomeropathies, which are characterized by a pattern of symptoms including generalized and specific lymphocytopenias as well as very short telomere length and disease anticipation. Methods: Because human LARP7 is the most likely ortholog of the Tetrahymena p65 protein, which is required for telomerase activity in that organism, we investigated the effects of LARP7 silencing in human cells as well as in two distinct families with Alazami syndrome (loss of function of LARP7). Results: Depletion of LARP7 caused a reduction in telomerase enzymatic activity and progressively shorter telomeres in human cancer cell lines. Alazami syndrome patients from two separate cohorts exhibited very short lymphocyte telomeres. Further, wild-type offspring of LARP7 mutant individuals also had very short telomeres, comparable to what is observed in telomerase (hTERT) mutant cohorts. Conclusions: Together, these experiments demonstrate that in addition to the readily apparent developmental disorder associated with LARP7 deficiency, an underlying telomeropathy exists even in unaffected siblings of these individuals.

UR - http://www.scopus.com/inward/record.url?scp=84992153356&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992153356&partnerID=8YFLogxK

U2 - 10.1186/s12864-016-3093-4

DO - 10.1186/s12864-016-3093-4

M3 - Article

VL - 17

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

M1 - 749

ER -