MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss

Guney Bademci; Clemer Abad; Armagan Incesulu; Abolfazl Rad; Ozgul Alper; Susanne M. Kolb; Filiz B. Cengiz; Oscar Diaz-Horta; Fatma Silan; Ercan Mihci; Emre Ocak; Maryam Najafi; Reza Maroofian; Elanur Yilmaz; Banu G. Nur; Duygu Duman; Shengru Guo; David W. Sant; Gaofeng Wang; Paula V. Monje; Thomas Haaf; Susan H. Blanton; Barbara Vona; Katherina Walz; Mustafa Tekin

doi:10.1007/s00439-018-1901-4

MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss

Guney Bademci, Clemer Abad, Armagan Incesulu, Abolfazl Rad, Ozgul Alper, Susanne M. Kolb, Filiz B. Cengiz, Oscar Diaz-Horta, Fatma Silan, Ercan Mihci, Emre Ocak, Maryam Najafi, Reza Maroofian, Elanur Yilmaz, Banu G. Nur, Duygu Duman, Shengru Guo, David W. Sant, Gaofeng Wang, Paula V. MonjeThomas Haaf, Susan H. Blanton, Barbara Vona, Katherina Walz, Mustafa Tekin

Neurosurgery

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

13 Scopus citations

Abstract

While recent studies have revealed a substantial portion of the genes underlying human hearing loss, the extensive genetic landscape has not been completely explored. Here, we report a loss-of-function variant (c.72delA) in MPZL2 in three unrelated multiplex families from Turkey and Iran with autosomal recessive nonsyndromic hearing loss. The variant co-segregates with moderate sensorineural hearing loss in all three families. We show a shared haplotype flanking the variant in our families implicating a single founder. While rare in other populations, the allele frequency of the variant is ~ 0.004 in Ashkenazi Jews, suggesting that it may be an important cause of moderate hearing loss in that population. We show that Mpzl2 is expressed in mouse inner ear, and the protein localizes in the auditory inner and outer hair cells, with an asymmetric subcellular localization. We thus present MPZL2 as a novel gene associated with sensorineural hearing loss.

Original language	English
Pages (from-to)	479-486
Number of pages	8
Journal	Human Genetics
Volume	137
Issue number	6-7
DOIs	https://doi.org/10.1007/s00439-018-1901-4
State	Published - Jul 1 2018

Bibliographical note

Funding Information:
Acknowledgements We are grateful to the families participating in this study. This study was supported by R01DC09645 and R01DC012836 from the National Institutes of Health/National Institute on Deafness and Other Communication Disorders to MT and DNA/Tissue Bank of Akdeniz University, Antalya, Turkey.

Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1007/s00439-018-1901-4

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Bademci, G., Abad, C., Incesulu, A., Rad, A., Alper, O., Kolb, S. M., Cengiz, F. B., Diaz-Horta, O., Silan, F., Mihci, E., Ocak, E., Najafi, M., Maroofian, R., Yilmaz, E., Nur, B. G., Duman, D., Guo, S., Sant, D. W., Wang, G., ... Tekin, M. (2018). MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss. Human Genetics, 137(6-7), 479-486. https://doi.org/10.1007/s00439-018-1901-4

@article{470531a59bb64f1e90979cf5fed8df37,

title = "MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss",

abstract = "While recent studies have revealed a substantial portion of the genes underlying human hearing loss, the extensive genetic landscape has not been completely explored. Here, we report a loss-of-function variant (c.72delA) in MPZL2 in three unrelated multiplex families from Turkey and Iran with autosomal recessive nonsyndromic hearing loss. The variant co-segregates with moderate sensorineural hearing loss in all three families. We show a shared haplotype flanking the variant in our families implicating a single founder. While rare in other populations, the allele frequency of the variant is ~ 0.004 in Ashkenazi Jews, suggesting that it may be an important cause of moderate hearing loss in that population. We show that Mpzl2 is expressed in mouse inner ear, and the protein localizes in the auditory inner and outer hair cells, with an asymmetric subcellular localization. We thus present MPZL2 as a novel gene associated with sensorineural hearing loss.",

author = "Guney Bademci and Clemer Abad and Armagan Incesulu and Abolfazl Rad and Ozgul Alper and Kolb, {Susanne M.} and Cengiz, {Filiz B.} and Oscar Diaz-Horta and Fatma Silan and Ercan Mihci and Emre Ocak and Maryam Najafi and Reza Maroofian and Elanur Yilmaz and Nur, {Banu G.} and Duygu Duman and Shengru Guo and Sant, {David W.} and Gaofeng Wang and Monje, {Paula V.} and Thomas Haaf and Blanton, {Susan H.} and Barbara Vona and Katherina Walz and Mustafa Tekin",

note = "Funding Information: Acknowledgements We are grateful to the families participating in this study. This study was supported by R01DC09645 and R01DC012836 from the National Institutes of Health/National Institute on Deafness and Other Communication Disorders to MT and DNA/Tissue Bank of Akdeniz University, Antalya, Turkey. Publisher Copyright: {\textcopyright} 2018, Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2018",

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doi = "10.1007/s00439-018-1901-4",

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Bademci, G, Abad, C, Incesulu, A, Rad, A, Alper, O, Kolb, SM, Cengiz, FB, Diaz-Horta, O, Silan, F, Mihci, E, Ocak, E, Najafi, M, Maroofian, R, Yilmaz, E, Nur, BG, Duman, D, Guo, S, Sant, DW, Wang, G, Monje, PV, Haaf, T, Blanton, SH, Vona, B, Walz, K & Tekin, M 2018, 'MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss', Human Genetics, vol. 137, no. 6-7, pp. 479-486. https://doi.org/10.1007/s00439-018-1901-4

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AU - Bademci, Guney

AU - Abad, Clemer

AU - Incesulu, Armagan

AU - Rad, Abolfazl

AU - Alper, Ozgul

AU - Kolb, Susanne M.

AU - Cengiz, Filiz B.

AU - Diaz-Horta, Oscar

AU - Silan, Fatma

AU - Mihci, Ercan

AU - Ocak, Emre

AU - Najafi, Maryam

AU - Maroofian, Reza

AU - Yilmaz, Elanur

AU - Nur, Banu G.

AU - Duman, Duygu

AU - Guo, Shengru

AU - Sant, David W.

AU - Wang, Gaofeng

AU - Monje, Paula V.

AU - Haaf, Thomas

AU - Blanton, Susan H.

AU - Vona, Barbara

AU - Walz, Katherina

AU - Tekin, Mustafa

N1 - Funding Information: Acknowledgements We are grateful to the families participating in this study. This study was supported by R01DC09645 and R01DC012836 from the National Institutes of Health/National Institute on Deafness and Other Communication Disorders to MT and DNA/Tissue Bank of Akdeniz University, Antalya, Turkey. Publisher Copyright: © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - While recent studies have revealed a substantial portion of the genes underlying human hearing loss, the extensive genetic landscape has not been completely explored. Here, we report a loss-of-function variant (c.72delA) in MPZL2 in three unrelated multiplex families from Turkey and Iran with autosomal recessive nonsyndromic hearing loss. The variant co-segregates with moderate sensorineural hearing loss in all three families. We show a shared haplotype flanking the variant in our families implicating a single founder. While rare in other populations, the allele frequency of the variant is ~ 0.004 in Ashkenazi Jews, suggesting that it may be an important cause of moderate hearing loss in that population. We show that Mpzl2 is expressed in mouse inner ear, and the protein localizes in the auditory inner and outer hair cells, with an asymmetric subcellular localization. We thus present MPZL2 as a novel gene associated with sensorineural hearing loss.

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MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss

Abstract

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