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CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder

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CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. / Wortmann, Saskia B; Ziętkiewicz, Szymon; Kousi, Maria; Szklarczyk, Radek; Haack, Tobias B; Gersting, Søren W; Muntau, Ania C; Rakovic, Aleksandar; Renkema, G Herma; Rodenburg, Richard J; Strom, Tim M; Meitinger, Thomas; Rubio-Gozalbo, M Estela; Chrusciel, Elzbieta; Distelmaier, Felix; Golzio, Christelle; Jansen, Joop H; van Karnebeek, Clara; Lillquist, Yolanda; Lücke, Thomas; Õunap, Katrin; Zordania, Riina; Yaplito-Lee, Joy; van Bokhoven, Hans; Spelbrink, Johannes N; Vaz, Frédéric M; Pras-Raves, Mia; Ploski, Rafal; Pronicka, Ewa; Klein, Christine; Willemsen, Michel A A P; de Brouwer, Arjan P M; Prokisch, Holger; Katsanis, Nicholas; Wevers, Ron A.

in: AM J HUM GENET, Jahrgang 96, Nr. 2, 05.02.2015, S. 245-57.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Wortmann, SB, Ziętkiewicz, S, Kousi, M, Szklarczyk, R, Haack, TB, Gersting, SW, Muntau, AC, Rakovic, A, Renkema, GH, Rodenburg, RJ, Strom, TM, Meitinger, T, Rubio-Gozalbo, ME, Chrusciel, E, Distelmaier, F, Golzio, C, Jansen, JH, van Karnebeek, C, Lillquist, Y, Lücke, T, Õunap, K, Zordania, R, Yaplito-Lee, J, van Bokhoven, H, Spelbrink, JN, Vaz, FM, Pras-Raves, M, Ploski, R, Pronicka, E, Klein, C, Willemsen, MAAP, de Brouwer, APM, Prokisch, H, Katsanis, N & Wevers, RA 2015, 'CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder', AM J HUM GENET, Jg. 96, Nr. 2, S. 245-57. https://doi.org/10.1016/j.ajhg.2014.12.013

APA

Wortmann, S. B., Ziętkiewicz, S., Kousi, M., Szklarczyk, R., Haack, T. B., Gersting, S. W., Muntau, A. C., Rakovic, A., Renkema, G. H., Rodenburg, R. J., Strom, T. M., Meitinger, T., Rubio-Gozalbo, M. E., Chrusciel, E., Distelmaier, F., Golzio, C., Jansen, J. H., van Karnebeek, C., Lillquist, Y., ... Wevers, R. A. (2015). CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. AM J HUM GENET, 96(2), 245-57. https://doi.org/10.1016/j.ajhg.2014.12.013

Vancouver

Wortmann SB, Ziętkiewicz S, Kousi M, Szklarczyk R, Haack TB, Gersting SW et al. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. AM J HUM GENET. 2015 Feb 5;96(2):245-57. https://doi.org/10.1016/j.ajhg.2014.12.013

Bibtex

@article{d25df8d66eb943278c1cf56a0de839dc,
title = "CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder",
abstract = "We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early death. Exome sequencing of two unrelated individuals and subsequent Sanger sequencing of 16 individuals with an overlapping phenotype identified a total of 14 rare, predicted deleterious alleles in CLPB in 14 individuals from 9 unrelated families. CLPB encodes caseinolytic peptidase B homolog ClpB, a member of the AAA+ protein family. To evaluate the relevance of CLPB in the pathogenesis of this syndrome, we developed a zebrafish model and an in vitro assay to measure ATPase activity. Suppression of clpb in zebrafish embryos induced a central nervous system phenotype that was consistent with cerebellar and cerebral atrophy that could be rescued by wild-type, but not mutant, human CLPB mRNA. Consistent with these data, the loss-of-function effect of one of the identified variants (c.1222A>G [p.Arg408Gly]) was supported further by in vitro evidence with the mutant peptides abolishing ATPase function. Additionally, we show that CLPB interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia (SCN) 3 (Kostmann disease [caused by HAX1 mutations]). Taken together, mutations in CLPB define a syndrome with intellectual disability, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria.",
keywords = "Abnormalities, Multiple, Adenosine Triphosphatases, Animals, Atrophy, Base Sequence, Brain, Cataract, Endopeptidase Clp, Exome, Humans, Intellectual Disability, Metabolism, Inborn Errors, Molecular Sequence Data, Movement Disorders, Neutropenia, Polymorphism, Single Nucleotide, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Sequence Analysis, DNA, Zebrafish",
author = "Wortmann, {Saskia B} and Szymon Zi{\c e}tkiewicz and Maria Kousi and Radek Szklarczyk and Haack, {Tobias B} and Gersting, {S{\o}ren W} and Muntau, {Ania C} and Aleksandar Rakovic and Renkema, {G Herma} and Rodenburg, {Richard J} and Strom, {Tim M} and Thomas Meitinger and Rubio-Gozalbo, {M Estela} and Elzbieta Chrusciel and Felix Distelmaier and Christelle Golzio and Jansen, {Joop H} and {van Karnebeek}, Clara and Yolanda Lillquist and Thomas L{\"u}cke and Katrin {\~O}unap and Riina Zordania and Joy Yaplito-Lee and {van Bokhoven}, Hans and Spelbrink, {Johannes N} and Vaz, {Fr{\'e}d{\'e}ric M} and Mia Pras-Raves and Rafal Ploski and Ewa Pronicka and Christine Klein and Willemsen, {Michel A A P} and {de Brouwer}, {Arjan P M} and Holger Prokisch and Nicholas Katsanis and Wevers, {Ron A}",
note = "Copyright {\textcopyright} 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.",
year = "2015",
month = feb,
day = "5",
doi = "10.1016/j.ajhg.2014.12.013",
language = "English",
volume = "96",
pages = "245--57",
journal = "AM J HUM GENET",
issn = "0002-9297",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder

AU - Wortmann, Saskia B

AU - Ziętkiewicz, Szymon

AU - Kousi, Maria

AU - Szklarczyk, Radek

AU - Haack, Tobias B

AU - Gersting, Søren W

AU - Muntau, Ania C

AU - Rakovic, Aleksandar

AU - Renkema, G Herma

AU - Rodenburg, Richard J

AU - Strom, Tim M

AU - Meitinger, Thomas

AU - Rubio-Gozalbo, M Estela

AU - Chrusciel, Elzbieta

AU - Distelmaier, Felix

AU - Golzio, Christelle

AU - Jansen, Joop H

AU - van Karnebeek, Clara

AU - Lillquist, Yolanda

AU - Lücke, Thomas

AU - Õunap, Katrin

AU - Zordania, Riina

AU - Yaplito-Lee, Joy

AU - van Bokhoven, Hans

AU - Spelbrink, Johannes N

AU - Vaz, Frédéric M

AU - Pras-Raves, Mia

AU - Ploski, Rafal

AU - Pronicka, Ewa

AU - Klein, Christine

AU - Willemsen, Michel A A P

AU - de Brouwer, Arjan P M

AU - Prokisch, Holger

AU - Katsanis, Nicholas

AU - Wevers, Ron A

N1 - Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

PY - 2015/2/5

Y1 - 2015/2/5

N2 - We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early death. Exome sequencing of two unrelated individuals and subsequent Sanger sequencing of 16 individuals with an overlapping phenotype identified a total of 14 rare, predicted deleterious alleles in CLPB in 14 individuals from 9 unrelated families. CLPB encodes caseinolytic peptidase B homolog ClpB, a member of the AAA+ protein family. To evaluate the relevance of CLPB in the pathogenesis of this syndrome, we developed a zebrafish model and an in vitro assay to measure ATPase activity. Suppression of clpb in zebrafish embryos induced a central nervous system phenotype that was consistent with cerebellar and cerebral atrophy that could be rescued by wild-type, but not mutant, human CLPB mRNA. Consistent with these data, the loss-of-function effect of one of the identified variants (c.1222A>G [p.Arg408Gly]) was supported further by in vitro evidence with the mutant peptides abolishing ATPase function. Additionally, we show that CLPB interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia (SCN) 3 (Kostmann disease [caused by HAX1 mutations]). Taken together, mutations in CLPB define a syndrome with intellectual disability, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria.

AB - We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early death. Exome sequencing of two unrelated individuals and subsequent Sanger sequencing of 16 individuals with an overlapping phenotype identified a total of 14 rare, predicted deleterious alleles in CLPB in 14 individuals from 9 unrelated families. CLPB encodes caseinolytic peptidase B homolog ClpB, a member of the AAA+ protein family. To evaluate the relevance of CLPB in the pathogenesis of this syndrome, we developed a zebrafish model and an in vitro assay to measure ATPase activity. Suppression of clpb in zebrafish embryos induced a central nervous system phenotype that was consistent with cerebellar and cerebral atrophy that could be rescued by wild-type, but not mutant, human CLPB mRNA. Consistent with these data, the loss-of-function effect of one of the identified variants (c.1222A>G [p.Arg408Gly]) was supported further by in vitro evidence with the mutant peptides abolishing ATPase function. Additionally, we show that CLPB interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia (SCN) 3 (Kostmann disease [caused by HAX1 mutations]). Taken together, mutations in CLPB define a syndrome with intellectual disability, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria.

KW - Abnormalities, Multiple

KW - Adenosine Triphosphatases

KW - Animals

KW - Atrophy

KW - Base Sequence

KW - Brain

KW - Cataract

KW - Endopeptidase Clp

KW - Exome

KW - Humans

KW - Intellectual Disability

KW - Metabolism, Inborn Errors

KW - Molecular Sequence Data

KW - Movement Disorders

KW - Neutropenia

KW - Polymorphism, Single Nucleotide

KW - Sarcoplasmic Reticulum Calcium-Transporting ATPases

KW - Sequence Analysis, DNA

KW - Zebrafish

U2 - 10.1016/j.ajhg.2014.12.013

DO - 10.1016/j.ajhg.2014.12.013

M3 - SCORING: Journal article

C2 - 25597510

VL - 96

SP - 245

EP - 257

JO - AM J HUM GENET

JF - AM J HUM GENET

SN - 0002-9297

IS - 2

ER -