A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy

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A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy. / Zazo Seco, Celia; Castells-Nobau, Anna; Joo, Seol-Hee; Schraders, Margit; Foo, Jia Nee; van der Voet, Monique; Velan, S Sendhil; Nijhof, Bonnie; Oostrik, Jaap; de Vrieze, Erik; Katana, Radoslaw; Mansoor, Atika; Huynen, Martijn; Szklarczyk, Radek; Oti, Martin; Tranebjærg, Lisbeth; van Wijk, Erwin; Scheffer-de Gooyert, Jolanda M; Siddique, Saadat; Baets, Jonathan; de Jonghe, Peter; Kazmi, Syed Ali Raza; Sadananthan, Suresh Anand; van de Warrenburg, Bart P; Khor, Chiea Chuen; Göpfert, Martin C; Qamar, Raheel; Schenck, Annette; Kremer, Hannie; Siddiqi, Saima.

I: Disease models & mechanisms, Bind 10, 02.2017, s. 105-118.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Zazo Seco, C, Castells-Nobau, A, Joo, S-H, Schraders, M, Foo, JN, van der Voet, M, Velan, SS, Nijhof, B, Oostrik, J, de Vrieze, E, Katana, R, Mansoor, A, Huynen, M, Szklarczyk, R, Oti, M, Tranebjærg, L, van Wijk, E, Scheffer-de Gooyert, JM, Siddique, S, Baets, J, de Jonghe, P, Kazmi, SAR, Sadananthan, SA, van de Warrenburg, BP, Khor, CC, Göpfert, MC, Qamar, R, Schenck, A, Kremer, H & Siddiqi, S 2017, 'A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy', Disease models & mechanisms, bind 10, s. 105-118. https://doi.org/10.1242/dmm.026476

APA

Zazo Seco, C., Castells-Nobau, A., Joo, S-H., Schraders, M., Foo, J. N., van der Voet, M., Velan, S. S., Nijhof, B., Oostrik, J., de Vrieze, E., Katana, R., Mansoor, A., Huynen, M., Szklarczyk, R., Oti, M., Tranebjærg, L., van Wijk, E., Scheffer-de Gooyert, J. M., Siddique, S., ... Siddiqi, S. (2017). A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy. Disease models & mechanisms, 10, 105-118. https://doi.org/10.1242/dmm.026476

Vancouver

Zazo Seco C, Castells-Nobau A, Joo S-H, Schraders M, Foo JN, van der Voet M o.a. A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy. Disease models & mechanisms. 2017 feb.;10:105-118. https://doi.org/10.1242/dmm.026476

Author

Zazo Seco, Celia ; Castells-Nobau, Anna ; Joo, Seol-Hee ; Schraders, Margit ; Foo, Jia Nee ; van der Voet, Monique ; Velan, S Sendhil ; Nijhof, Bonnie ; Oostrik, Jaap ; de Vrieze, Erik ; Katana, Radoslaw ; Mansoor, Atika ; Huynen, Martijn ; Szklarczyk, Radek ; Oti, Martin ; Tranebjærg, Lisbeth ; van Wijk, Erwin ; Scheffer-de Gooyert, Jolanda M ; Siddique, Saadat ; Baets, Jonathan ; de Jonghe, Peter ; Kazmi, Syed Ali Raza ; Sadananthan, Suresh Anand ; van de Warrenburg, Bart P ; Khor, Chiea Chuen ; Göpfert, Martin C ; Qamar, Raheel ; Schenck, Annette ; Kremer, Hannie ; Siddiqi, Saima. / A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy. I: Disease models & mechanisms. 2017 ; Bind 10. s. 105-118.

Bibtex

@article{fd1f9f1322ed4945a53626993cf362b5,
title = "A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy",
abstract = "A consanguineous family from Pakistan was ascertained to have a novel deafness-dystonia syndrome with motor regression, ichthyosis-like features and signs of sensory neuropathy. By applying a combined strategy of linkage analysis and whole-exome sequencing in the presented family, a homozygous nonsense mutation, c.4G>T (p.Glu2*), in FITM2 was identified. FITM2 and its paralog FITM1 constitute an evolutionary conserved protein family involved in partitioning of triglycerides into cellular lipid droplets. Despite the role of FITM2 in neutral lipid storage and metabolism, no indications for lipodystrophy were observed in the affected individuals. In order to obtain independent evidence for the involvement of FITM2 in the human pathology, downregulation of the single Fitm ortholog, CG10671, in Drosophila melanogaster was pursued using RNA interference. Characteristics of the syndrome, including progressive locomotor impairment, hearing loss and disturbed sensory functions, were recapitulated in Drosophila, which supports the causative nature of the FITM2 mutation. Mutation-based genetic counseling can now be provided to the family and insight is obtained into the potential impact of genetic variation in FITM2.",
keywords = "Adiposity, Animals, Audiometry, Pure-Tone, Base Sequence, Child, Codon, Nonsense/genetics, Deaf-Blind Disorders/blood, Disease Models, Animal, Drosophila Proteins/genetics, Drosophila melanogaster/genetics, Dystonia/blood, Female, Gene Expression Regulation, Gene Knockdown Techniques, HEK293 Cells, Hearing Loss/genetics, Homozygote, Humans, Ichthyosis/complications, Intellectual Disability/blood, Lipid Droplets/metabolism, Liver/metabolism, Locomotion, Male, Membrane Proteins/genetics, Motor Activity, Mutation/genetics, Optic Atrophy/blood, Pedigree, Sensory Receptor Cells/pathology, Whole Exome Sequencing, Young Adult",
author = "{Zazo Seco}, Celia and Anna Castells-Nobau and Seol-Hee Joo and Margit Schraders and Foo, {Jia Nee} and {van der Voet}, Monique and Velan, {S Sendhil} and Bonnie Nijhof and Jaap Oostrik and {de Vrieze}, Erik and Radoslaw Katana and Atika Mansoor and Martijn Huynen and Radek Szklarczyk and Martin Oti and Lisbeth Tranebj{\ae}rg and {van Wijk}, Erwin and {Scheffer-de Gooyert}, {Jolanda M} and Saadat Siddique and Jonathan Baets and {de Jonghe}, Peter and Kazmi, {Syed Ali Raza} and Sadananthan, {Suresh Anand} and {van de Warrenburg}, {Bart P} and Khor, {Chiea Chuen} and G{\"o}pfert, {Martin C} and Raheel Qamar and Annette Schenck and Hannie Kremer and Saima Siddiqi",
note = "{\textcopyright} 2017. Published by The Company of Biologists Ltd.",
year = "2017",
month = feb,
doi = "10.1242/dmm.026476",
language = "English",
volume = "10",
pages = "105--118",
journal = "Disease Models & Mechanisms",
issn = "1754-8403",
publisher = "company of biologists",

}

RIS

TY - JOUR

T1 - A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy

AU - Zazo Seco, Celia

AU - Castells-Nobau, Anna

AU - Joo, Seol-Hee

AU - Schraders, Margit

AU - Foo, Jia Nee

AU - van der Voet, Monique

AU - Velan, S Sendhil

AU - Nijhof, Bonnie

AU - Oostrik, Jaap

AU - de Vrieze, Erik

AU - Katana, Radoslaw

AU - Mansoor, Atika

AU - Huynen, Martijn

AU - Szklarczyk, Radek

AU - Oti, Martin

AU - Tranebjærg, Lisbeth

AU - van Wijk, Erwin

AU - Scheffer-de Gooyert, Jolanda M

AU - Siddique, Saadat

AU - Baets, Jonathan

AU - de Jonghe, Peter

AU - Kazmi, Syed Ali Raza

AU - Sadananthan, Suresh Anand

AU - van de Warrenburg, Bart P

AU - Khor, Chiea Chuen

AU - Göpfert, Martin C

AU - Qamar, Raheel

AU - Schenck, Annette

AU - Kremer, Hannie

AU - Siddiqi, Saima

N1 - © 2017. Published by The Company of Biologists Ltd.

PY - 2017/2

Y1 - 2017/2

N2 - A consanguineous family from Pakistan was ascertained to have a novel deafness-dystonia syndrome with motor regression, ichthyosis-like features and signs of sensory neuropathy. By applying a combined strategy of linkage analysis and whole-exome sequencing in the presented family, a homozygous nonsense mutation, c.4G>T (p.Glu2*), in FITM2 was identified. FITM2 and its paralog FITM1 constitute an evolutionary conserved protein family involved in partitioning of triglycerides into cellular lipid droplets. Despite the role of FITM2 in neutral lipid storage and metabolism, no indications for lipodystrophy were observed in the affected individuals. In order to obtain independent evidence for the involvement of FITM2 in the human pathology, downregulation of the single Fitm ortholog, CG10671, in Drosophila melanogaster was pursued using RNA interference. Characteristics of the syndrome, including progressive locomotor impairment, hearing loss and disturbed sensory functions, were recapitulated in Drosophila, which supports the causative nature of the FITM2 mutation. Mutation-based genetic counseling can now be provided to the family and insight is obtained into the potential impact of genetic variation in FITM2.

AB - A consanguineous family from Pakistan was ascertained to have a novel deafness-dystonia syndrome with motor regression, ichthyosis-like features and signs of sensory neuropathy. By applying a combined strategy of linkage analysis and whole-exome sequencing in the presented family, a homozygous nonsense mutation, c.4G>T (p.Glu2*), in FITM2 was identified. FITM2 and its paralog FITM1 constitute an evolutionary conserved protein family involved in partitioning of triglycerides into cellular lipid droplets. Despite the role of FITM2 in neutral lipid storage and metabolism, no indications for lipodystrophy were observed in the affected individuals. In order to obtain independent evidence for the involvement of FITM2 in the human pathology, downregulation of the single Fitm ortholog, CG10671, in Drosophila melanogaster was pursued using RNA interference. Characteristics of the syndrome, including progressive locomotor impairment, hearing loss and disturbed sensory functions, were recapitulated in Drosophila, which supports the causative nature of the FITM2 mutation. Mutation-based genetic counseling can now be provided to the family and insight is obtained into the potential impact of genetic variation in FITM2.

KW - Adiposity

KW - Animals

KW - Audiometry, Pure-Tone

KW - Base Sequence

KW - Child

KW - Codon, Nonsense/genetics

KW - Deaf-Blind Disorders/blood

KW - Disease Models, Animal

KW - Drosophila Proteins/genetics

KW - Drosophila melanogaster/genetics

KW - Dystonia/blood

KW - Female

KW - Gene Expression Regulation

KW - Gene Knockdown Techniques

KW - HEK293 Cells

KW - Hearing Loss/genetics

KW - Homozygote

KW - Humans

KW - Ichthyosis/complications

KW - Intellectual Disability/blood

KW - Lipid Droplets/metabolism

KW - Liver/metabolism

KW - Locomotion

KW - Male

KW - Membrane Proteins/genetics

KW - Motor Activity

KW - Mutation/genetics

KW - Optic Atrophy/blood

KW - Pedigree

KW - Sensory Receptor Cells/pathology

KW - Whole Exome Sequencing

KW - Young Adult

U2 - 10.1242/dmm.026476

DO - 10.1242/dmm.026476

M3 - Journal article

C2 - 28067622

VL - 10

SP - 105

EP - 118

JO - Disease Models & Mechanisms

JF - Disease Models & Mechanisms

SN - 1754-8403

ER -

ID: 195549376