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Functional Assessment of Variants Associated with Wolfram Syndrome

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Harvard

Riachi, M, Yilmaz, S, Kurnaz, E, Aycan, Z, Çetinkaya, S, Tranebjærg, L, Rendtorff, ND, Bitner-Glindzicz, M, Bockenhauer, D & Hussain, K 2019, 'Functional Assessment of Variants Associated with Wolfram Syndrome' Human Molecular Genetics, vol. 28, no. 22, pp. 3815-3824. https://doi.org/10.1093/hmg/ddz212

APA

Riachi, M., Yilmaz, S., Kurnaz, E., Aycan, Z., Çetinkaya, S., Tranebjærg, L., ... Hussain, K. (2019). Functional Assessment of Variants Associated with Wolfram Syndrome. Human Molecular Genetics, 28(22), 3815-3824. https://doi.org/10.1093/hmg/ddz212

CBE

Riachi M, Yilmaz S, Kurnaz E, Aycan Z, Çetinkaya S, Tranebjærg L, Rendtorff ND, Bitner-Glindzicz M, Bockenhauer D, Hussain K. 2019. Functional Assessment of Variants Associated with Wolfram Syndrome. Human Molecular Genetics. 28(22):3815-3824. https://doi.org/10.1093/hmg/ddz212

MLA

Vancouver

Riachi M, Yilmaz S, Kurnaz E, Aycan Z, Çetinkaya S, Tranebjærg L et al. Functional Assessment of Variants Associated with Wolfram Syndrome. Human Molecular Genetics. 2019 Nov 15;28(22):3815-3824. https://doi.org/10.1093/hmg/ddz212

Author

Riachi, Melissa ; Yilmaz, Sebahat ; Kurnaz, Erdal ; Aycan, Zehra ; Çetinkaya, Semra ; Tranebjærg, Lisbeth ; Rendtorff, Nanna Dahl ; Bitner-Glindzicz, Maria ; Bockenhauer, Detlef ; Hussain, Khalid. / Functional Assessment of Variants Associated with Wolfram Syndrome. In: Human Molecular Genetics. 2019 ; Vol. 28, No. 22. pp. 3815-3824.

Bibtex

@article{adc19430e71540c4873413a2c6dcfcf7,
title = "Functional Assessment of Variants Associated with Wolfram Syndrome",
abstract = "Wolfram Syndrome (WS) is a heterogeneous multisystem neurodegenerative disorder with two allelic variations in addition to a separate subtype known as WS type 2. The wide phenotypic spectrum of WS includes diabetes mellitus and optic atrophy which is often accompanied by diabetes insipidus, deafness, urological and neurological complications in combination or in isolation. To date, the understanding of the genotype phenotype relationship in this complex syndrome remains poorly understood. In this study we identified and explored the functionality of rare and novel variants in the two causative WS genes WFS1 and CISD2 by assessing the effects of the mutations on the encoded proteins Wolframin and ERIS, in a cohort of 12 patients with autosomal recessive WS, dominant WS and WS type 2. The identified pathogenic variants included missense changes, frameshift deletions and insertions in WFS1 and an exonic deletion in CISD2 which all altered the respective encoded protein in a manner that did not correlate to the phenome previously described. These observations suggest the lack of genotype phenotype correlation in this complex syndrome and the need to explore other molecular genetic mechanisms. Additionally, our findings highlight the importance of functionally assessing variants for their pathogenicity to tackle the problem of increasing variants of unknown significance (VUS) in the public genetic databases.",
author = "Melissa Riachi and Sebahat Yilmaz and Erdal Kurnaz and Zehra Aycan and Semra {\cC}etinkaya and Lisbeth Tranebj{\ae}rg and Rendtorff, {Nanna Dahl} and Maria Bitner-Glindzicz and Detlef Bockenhauer and Khalid Hussain",
note = "{\circledC} The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.",
year = "2019",
month = "11",
day = "15",
doi = "10.1093/hmg/ddz212",
language = "English",
volume = "28",
pages = "3815--3824",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "22",

}

RIS

TY - JOUR

T1 - Functional Assessment of Variants Associated with Wolfram Syndrome

AU - Riachi, Melissa

AU - Yilmaz, Sebahat

AU - Kurnaz, Erdal

AU - Aycan, Zehra

AU - Çetinkaya, Semra

AU - Tranebjærg, Lisbeth

AU - Rendtorff, Nanna Dahl

AU - Bitner-Glindzicz, Maria

AU - Bockenhauer, Detlef

AU - Hussain, Khalid

N1 - © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2019/11/15

Y1 - 2019/11/15

N2 - Wolfram Syndrome (WS) is a heterogeneous multisystem neurodegenerative disorder with two allelic variations in addition to a separate subtype known as WS type 2. The wide phenotypic spectrum of WS includes diabetes mellitus and optic atrophy which is often accompanied by diabetes insipidus, deafness, urological and neurological complications in combination or in isolation. To date, the understanding of the genotype phenotype relationship in this complex syndrome remains poorly understood. In this study we identified and explored the functionality of rare and novel variants in the two causative WS genes WFS1 and CISD2 by assessing the effects of the mutations on the encoded proteins Wolframin and ERIS, in a cohort of 12 patients with autosomal recessive WS, dominant WS and WS type 2. The identified pathogenic variants included missense changes, frameshift deletions and insertions in WFS1 and an exonic deletion in CISD2 which all altered the respective encoded protein in a manner that did not correlate to the phenome previously described. These observations suggest the lack of genotype phenotype correlation in this complex syndrome and the need to explore other molecular genetic mechanisms. Additionally, our findings highlight the importance of functionally assessing variants for their pathogenicity to tackle the problem of increasing variants of unknown significance (VUS) in the public genetic databases.

AB - Wolfram Syndrome (WS) is a heterogeneous multisystem neurodegenerative disorder with two allelic variations in addition to a separate subtype known as WS type 2. The wide phenotypic spectrum of WS includes diabetes mellitus and optic atrophy which is often accompanied by diabetes insipidus, deafness, urological and neurological complications in combination or in isolation. To date, the understanding of the genotype phenotype relationship in this complex syndrome remains poorly understood. In this study we identified and explored the functionality of rare and novel variants in the two causative WS genes WFS1 and CISD2 by assessing the effects of the mutations on the encoded proteins Wolframin and ERIS, in a cohort of 12 patients with autosomal recessive WS, dominant WS and WS type 2. The identified pathogenic variants included missense changes, frameshift deletions and insertions in WFS1 and an exonic deletion in CISD2 which all altered the respective encoded protein in a manner that did not correlate to the phenome previously described. These observations suggest the lack of genotype phenotype correlation in this complex syndrome and the need to explore other molecular genetic mechanisms. Additionally, our findings highlight the importance of functionally assessing variants for their pathogenicity to tackle the problem of increasing variants of unknown significance (VUS) in the public genetic databases.

U2 - 10.1093/hmg/ddz212

DO - 10.1093/hmg/ddz212

M3 - Journal article

VL - 28

SP - 3815

EP - 3824

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 22

ER -

ID: 58250790