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POPDC3 Gene Variants Associate with a New Form of Limb Girdle Muscular Dystrophy

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Harvard

Vissing, J, Johnson, K, Töpf, A, Nafissi, S, Díaz-Manera, J, French, VM, Schindler, RF, Sarathchandra, P, Løkken, N, Rinné, S, Freund, M, Decher, N, Müller, T, Duno, M, Krag, T, Brand, T & Straub, V 2019, 'POPDC3 Gene Variants Associate with a New Form of Limb Girdle Muscular Dystrophy' Annals of Neurology, bind 86, nr. 6, s. 832-843. https://doi.org/10.1002/ana.25620

APA

Vissing, J., Johnson, K., Töpf, A., Nafissi, S., Díaz-Manera, J., French, V. M., ... Straub, V. (2019). POPDC3 Gene Variants Associate with a New Form of Limb Girdle Muscular Dystrophy. Annals of Neurology, 86(6), 832-843. https://doi.org/10.1002/ana.25620

CBE

Vissing J, Johnson K, Töpf A, Nafissi S, Díaz-Manera J, French VM, Schindler RF, Sarathchandra P, Løkken N, Rinné S, Freund M, Decher N, Müller T, Duno M, Krag T, Brand T, Straub V. 2019. POPDC3 Gene Variants Associate with a New Form of Limb Girdle Muscular Dystrophy. Annals of Neurology. 86(6):832-843. https://doi.org/10.1002/ana.25620

MLA

Vancouver

Author

Vissing, John ; Johnson, Katherine ; Töpf, Ana ; Nafissi, Shahriar ; Díaz-Manera, Jordi ; French, Vanessa M ; Schindler, Roland F ; Sarathchandra, Padmini ; Løkken, Nicoline ; Rinné, Susanne ; Freund, Max ; Decher, Niels ; Müller, Thomas ; Duno, Morten ; Krag, Thomas ; Brand, Thomas ; Straub, Volker. / POPDC3 Gene Variants Associate with a New Form of Limb Girdle Muscular Dystrophy. I: Annals of Neurology. 2019 ; Bind 86, Nr. 6. s. 832-843.

Bibtex

@article{b8bf6f2db0194981b829a07e648b08f3,
title = "POPDC3 Gene Variants Associate with a New Form of Limb Girdle Muscular Dystrophy",
abstract = "OBJECTIVE: The Popeye domain containing 3 (POPDC3) gene encodes a membrane protein involved in cyclic adenosine monophosphate (cAMP) signaling. Besides gastric cancer, no disease association has been described. We describe a new muscular dystrophy associated with this gene.METHODS: We screened 1,500 patients with unclassified limb girdle weakness or hyperCKemia for pathogenic POPDC3 variants. Five patients carrying POPDC3 variants were examined by muscle magnetic resonance imaging (MRI), muscle biopsy, and cardiac examination. We performed functional analyses in a zebrafish popdc3 knockdown model and heterologous expression of the mutant proteins in Xenopus laevis oocytes to measure TREK-1 current.RESULTS: We identified homozygous POPDC3 missense variants (p.Leu155His, p.Leu217Phe, and p.Arg261Gln) in 5 patients from 3 ethnically distinct families. Variants affected highly conserved residues in the Popeye (p.Leu155 and p.Leu217) and carboxy-terminal (p.Arg261) domains. The variants were almost absent from control populations. Probands' muscle biopsies were dystrophic, and serum creatine kinase levels were 1,050 to 9,200U/l. Muscle weakness was proximal with adulthood onset in most patients and affected lower earlier than upper limbs. Muscle MRI revealed fat replacement of paraspinal and proximal leg muscles; cardiac investigations were unremarkable. Knockdown of popdc3 in zebrafish, using 2 different splice-site blocking morpholinos, resulted in larvae with tail curling and dystrophic muscle features. All 3 mutants cloned in Xenopus oocytes caused an aberrant modulation of the mechano-gated potassium channel, TREK-1.INTERPRETATION: Our findings point to an important role of POPDC3 for skeletal muscle function and suggest that pathogenic variants in POPDC3 are responsible for a novel type of autosomal recessive limb girdle muscular dystrophy. ANN NEUROL 2019.",
author = "John Vissing and Katherine Johnson and Ana T{\"o}pf and Shahriar Nafissi and Jordi D{\'i}az-Manera and French, {Vanessa M} and Schindler, {Roland F} and Padmini Sarathchandra and Nicoline L{\o}kken and Susanne Rinn{\'e} and Max Freund and Niels Decher and Thomas M{\"u}ller and Morten Duno and Thomas Krag and Thomas Brand and Volker Straub",
note = "{\circledC} 2019 American Neurological Association.",
year = "2019",
month = "12",
doi = "10.1002/ana.25620",
language = "English",
volume = "86",
pages = "832--843",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John/Wiley & Sons, Inc. John/Wiley & Sons Ltd",
number = "6",

}

RIS

TY - JOUR

T1 - POPDC3 Gene Variants Associate with a New Form of Limb Girdle Muscular Dystrophy

AU - Vissing, John

AU - Johnson, Katherine

AU - Töpf, Ana

AU - Nafissi, Shahriar

AU - Díaz-Manera, Jordi

AU - French, Vanessa M

AU - Schindler, Roland F

AU - Sarathchandra, Padmini

AU - Løkken, Nicoline

AU - Rinné, Susanne

AU - Freund, Max

AU - Decher, Niels

AU - Müller, Thomas

AU - Duno, Morten

AU - Krag, Thomas

AU - Brand, Thomas

AU - Straub, Volker

N1 - © 2019 American Neurological Association.

PY - 2019/12

Y1 - 2019/12

N2 - OBJECTIVE: The Popeye domain containing 3 (POPDC3) gene encodes a membrane protein involved in cyclic adenosine monophosphate (cAMP) signaling. Besides gastric cancer, no disease association has been described. We describe a new muscular dystrophy associated with this gene.METHODS: We screened 1,500 patients with unclassified limb girdle weakness or hyperCKemia for pathogenic POPDC3 variants. Five patients carrying POPDC3 variants were examined by muscle magnetic resonance imaging (MRI), muscle biopsy, and cardiac examination. We performed functional analyses in a zebrafish popdc3 knockdown model and heterologous expression of the mutant proteins in Xenopus laevis oocytes to measure TREK-1 current.RESULTS: We identified homozygous POPDC3 missense variants (p.Leu155His, p.Leu217Phe, and p.Arg261Gln) in 5 patients from 3 ethnically distinct families. Variants affected highly conserved residues in the Popeye (p.Leu155 and p.Leu217) and carboxy-terminal (p.Arg261) domains. The variants were almost absent from control populations. Probands' muscle biopsies were dystrophic, and serum creatine kinase levels were 1,050 to 9,200U/l. Muscle weakness was proximal with adulthood onset in most patients and affected lower earlier than upper limbs. Muscle MRI revealed fat replacement of paraspinal and proximal leg muscles; cardiac investigations were unremarkable. Knockdown of popdc3 in zebrafish, using 2 different splice-site blocking morpholinos, resulted in larvae with tail curling and dystrophic muscle features. All 3 mutants cloned in Xenopus oocytes caused an aberrant modulation of the mechano-gated potassium channel, TREK-1.INTERPRETATION: Our findings point to an important role of POPDC3 for skeletal muscle function and suggest that pathogenic variants in POPDC3 are responsible for a novel type of autosomal recessive limb girdle muscular dystrophy. ANN NEUROL 2019.

AB - OBJECTIVE: The Popeye domain containing 3 (POPDC3) gene encodes a membrane protein involved in cyclic adenosine monophosphate (cAMP) signaling. Besides gastric cancer, no disease association has been described. We describe a new muscular dystrophy associated with this gene.METHODS: We screened 1,500 patients with unclassified limb girdle weakness or hyperCKemia for pathogenic POPDC3 variants. Five patients carrying POPDC3 variants were examined by muscle magnetic resonance imaging (MRI), muscle biopsy, and cardiac examination. We performed functional analyses in a zebrafish popdc3 knockdown model and heterologous expression of the mutant proteins in Xenopus laevis oocytes to measure TREK-1 current.RESULTS: We identified homozygous POPDC3 missense variants (p.Leu155His, p.Leu217Phe, and p.Arg261Gln) in 5 patients from 3 ethnically distinct families. Variants affected highly conserved residues in the Popeye (p.Leu155 and p.Leu217) and carboxy-terminal (p.Arg261) domains. The variants were almost absent from control populations. Probands' muscle biopsies were dystrophic, and serum creatine kinase levels were 1,050 to 9,200U/l. Muscle weakness was proximal with adulthood onset in most patients and affected lower earlier than upper limbs. Muscle MRI revealed fat replacement of paraspinal and proximal leg muscles; cardiac investigations were unremarkable. Knockdown of popdc3 in zebrafish, using 2 different splice-site blocking morpholinos, resulted in larvae with tail curling and dystrophic muscle features. All 3 mutants cloned in Xenopus oocytes caused an aberrant modulation of the mechano-gated potassium channel, TREK-1.INTERPRETATION: Our findings point to an important role of POPDC3 for skeletal muscle function and suggest that pathogenic variants in POPDC3 are responsible for a novel type of autosomal recessive limb girdle muscular dystrophy. ANN NEUROL 2019.

U2 - 10.1002/ana.25620

DO - 10.1002/ana.25620

M3 - Journal article

VL - 86

SP - 832

EP - 843

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 6

ER -

ID: 58279246