Limb girdle muscular dystrophy due to mutations in POMT2

Sofie Thurø Østergaard; Katherine Johnson; Tanya Stojkovic; Thomas Krag; Willem De Ridder; Peter De Jonghe; Jonathan Baets; Kristl G Claeys; Roberto Fernández-Torrón; Lauren Phillips; Ana Topf; Jaume Colomer; Shahriar Nafissi; Shirin Jamal-Omidi; Celine Bouchet-Seraphin; France Leturcq; Daniel G MacArthur; Monkol Lek; Liwen Xu; Isabelle Nelson; Volker Straub; John Vissing

doi:10.1136/jnnp-2017-317018

Limb girdle muscular dystrophy due to mutations in POMT2

Sofie Thurø Østergaard, Katherine Johnson, Tanya Stojkovic, Thomas Krag, Willem De Ridder, Peter De Jonghe, Jonathan Baets, Kristl G Claeys, Roberto Fernández-Torrón, Lauren Phillips, Ana Topf, Jaume Colomer, Shahriar Nafissi, Shirin Jamal-Omidi, Celine Bouchet-Seraphin, France Leturcq, Daniel G MacArthur, Monkol Lek, Liwen Xu, Isabelle NelsonVolker Straub, John Vissing

Department of Clinical Medicine

9 Citations (Scopus)

Abstract

BACKGROUND: Mutations in the gene coding for protein O-mannosyl-transferase 2 (POMT2) are known to cause severe congenital muscular dystrophy, and recently, mutations in POMT2 have also been linked to a milder limb-girdle muscular dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N). Only four cases have been reported so far.ClinicalTrials.gov ID: NCT02759302 METHODS: We report 12 new cases of LGMD2N, aged 18-63 years. Muscle involvement was assessed by MRI, muscle strength testing and muscle biopsy analysis. Other clinical features were also recorded.

RESULTS: Presenting symptoms were difficulties in walking, pain during exercise, delayed motor milestones and learning disabilities at school. All had some degree of cognitive impairment. Brain MRIs were abnormal in 3 of 10 patients, showing ventricular enlargement in one, periventricular hyperintensities in another and frontal atrophy of the left hemisphere in a third patient. Most affected muscle groups were hip and knee flexors and extensors on strength testing. On MRI, most affected muscles were hamstrings followed by paraspinal and gluteal muscles. The 12 patients in our cohort carried 11 alleles with known mutations, whereas 11 novel mutations accounted for the remaining 13 alleles.

CONCLUSION: We describe the first cohort of patients with LGMD2N and show that unlike other LGMD types, all patients had cognitive impairment. Primary muscle involvement was found in hamstring, paraspinal and gluteal muscles on MRI, which correlated well with reduced muscle strength in hip and knee flexors and extensors. The study expands the mutational spectrum for LGMD2N, with the description of 11 novel POMT2 mutations in the association with LGMD2N.

CLINICAL TRIAL REGISTRATION: NCT02759302.

Original language	English
Journal	Journal of neurology, neurosurgery, and psychiatry
Volume	89
Issue number	5
Pages (from-to)	506-512
ISSN	0022-3050
DOIs	https://doi.org/10.1136/jnnp-2017-317018
Publication status	Published - 1 May 2018

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Østergaard, S. T., Johnson, K., Stojkovic, T., Krag, T., De Ridder, W., De Jonghe, P., Baets, J., Claeys, K. G., Fernández-Torrón, R., Phillips, L., Topf, A., Colomer, J., Nafissi, S., Jamal-Omidi, S., Bouchet-Seraphin, C., Leturcq, F., MacArthur, D. G., Lek, M., Xu, L., ... Vissing, J. (2018). Limb girdle muscular dystrophy due to mutations in POMT2. Journal of neurology, neurosurgery, and psychiatry, 89(5), 506-512. https://doi.org/10.1136/jnnp-2017-317018

Østergaard, ST, Johnson, K, Stojkovic, T, Krag, T, De Ridder, W, De Jonghe, P, Baets, J, Claeys, KG, Fernández-Torrón, R, Phillips, L, Topf, A, Colomer, J, Nafissi, S, Jamal-Omidi, S, Bouchet-Seraphin, C, Leturcq, F, MacArthur, DG, Lek, M, Xu, L, Nelson, I, Straub, V & Vissing, J 2018, 'Limb girdle muscular dystrophy due to mutations in POMT2', Journal of neurology, neurosurgery, and psychiatry, vol. 89, no. 5, pp. 506-512. https://doi.org/10.1136/jnnp-2017-317018

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title = "Limb girdle muscular dystrophy due to mutations in POMT2",

abstract = "BACKGROUND: Mutations in the gene coding for protein O-mannosyl-transferase 2 (POMT2) are known to cause severe congenital muscular dystrophy, and recently, mutations in POMT2 have also been linked to a milder limb-girdle muscular dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N). Only four cases have been reported so far.ClinicalTrials.gov ID: NCT02759302 METHODS: We report 12 new cases of LGMD2N, aged 18-63 years. Muscle involvement was assessed by MRI, muscle strength testing and muscle biopsy analysis. Other clinical features were also recorded.RESULTS: Presenting symptoms were difficulties in walking, pain during exercise, delayed motor milestones and learning disabilities at school. All had some degree of cognitive impairment. Brain MRIs were abnormal in 3 of 10 patients, showing ventricular enlargement in one, periventricular hyperintensities in another and frontal atrophy of the left hemisphere in a third patient. Most affected muscle groups were hip and knee flexors and extensors on strength testing. On MRI, most affected muscles were hamstrings followed by paraspinal and gluteal muscles. The 12 patients in our cohort carried 11 alleles with known mutations, whereas 11 novel mutations accounted for the remaining 13 alleles.CONCLUSION: We describe the first cohort of patients with LGMD2N and show that unlike other LGMD types, all patients had cognitive impairment. Primary muscle involvement was found in hamstring, paraspinal and gluteal muscles on MRI, which correlated well with reduced muscle strength in hip and knee flexors and extensors. The study expands the mutational spectrum for LGMD2N, with the description of 11 novel POMT2 mutations in the association with LGMD2N.CLINICAL TRIAL REGISTRATION: NCT02759302.",

author = "{\O}stergaard, {Sofie Thur{\o}} and Katherine Johnson and Tanya Stojkovic and Thomas Krag and {De Ridder}, Willem and {De Jonghe}, Peter and Jonathan Baets and Claeys, {Kristl G} and Roberto Fern{\'a}ndez-Torr{\'o}n and Lauren Phillips and Ana Topf and Jaume Colomer and Shahriar Nafissi and Shirin Jamal-Omidi and Celine Bouchet-Seraphin and France Leturcq and MacArthur, {Daniel G} and Monkol Lek and Liwen Xu and Isabelle Nelson and Volker Straub and John Vissing",

note = "{\textcopyright} Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.",

year = "2018",

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doi = "10.1136/jnnp-2017-317018",

language = "English",

volume = "89",

pages = "506--512",

journal = "Journal of Neurology, Neurosurgery and Psychiatry",

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TY - JOUR

T1 - Limb girdle muscular dystrophy due to mutations in POMT2

AU - Østergaard, Sofie Thurø

AU - Johnson, Katherine

AU - Stojkovic, Tanya

AU - Krag, Thomas

AU - De Ridder, Willem

AU - De Jonghe, Peter

AU - Baets, Jonathan

AU - Claeys, Kristl G

AU - Fernández-Torrón, Roberto

AU - Phillips, Lauren

AU - Topf, Ana

AU - Colomer, Jaume

AU - Nafissi, Shahriar

AU - Jamal-Omidi, Shirin

AU - Bouchet-Seraphin, Celine

AU - Leturcq, France

AU - MacArthur, Daniel G

AU - Lek, Monkol

AU - Xu, Liwen

AU - Nelson, Isabelle

AU - Straub, Volker

AU - Vissing, John

PY - 2018/5/1

Y1 - 2018/5/1

N2 - BACKGROUND: Mutations in the gene coding for protein O-mannosyl-transferase 2 (POMT2) are known to cause severe congenital muscular dystrophy, and recently, mutations in POMT2 have also been linked to a milder limb-girdle muscular dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N). Only four cases have been reported so far.ClinicalTrials.gov ID: NCT02759302 METHODS: We report 12 new cases of LGMD2N, aged 18-63 years. Muscle involvement was assessed by MRI, muscle strength testing and muscle biopsy analysis. Other clinical features were also recorded.RESULTS: Presenting symptoms were difficulties in walking, pain during exercise, delayed motor milestones and learning disabilities at school. All had some degree of cognitive impairment. Brain MRIs were abnormal in 3 of 10 patients, showing ventricular enlargement in one, periventricular hyperintensities in another and frontal atrophy of the left hemisphere in a third patient. Most affected muscle groups were hip and knee flexors and extensors on strength testing. On MRI, most affected muscles were hamstrings followed by paraspinal and gluteal muscles. The 12 patients in our cohort carried 11 alleles with known mutations, whereas 11 novel mutations accounted for the remaining 13 alleles.CONCLUSION: We describe the first cohort of patients with LGMD2N and show that unlike other LGMD types, all patients had cognitive impairment. Primary muscle involvement was found in hamstring, paraspinal and gluteal muscles on MRI, which correlated well with reduced muscle strength in hip and knee flexors and extensors. The study expands the mutational spectrum for LGMD2N, with the description of 11 novel POMT2 mutations in the association with LGMD2N.CLINICAL TRIAL REGISTRATION: NCT02759302.

AB - BACKGROUND: Mutations in the gene coding for protein O-mannosyl-transferase 2 (POMT2) are known to cause severe congenital muscular dystrophy, and recently, mutations in POMT2 have also been linked to a milder limb-girdle muscular dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N). Only four cases have been reported so far.ClinicalTrials.gov ID: NCT02759302 METHODS: We report 12 new cases of LGMD2N, aged 18-63 years. Muscle involvement was assessed by MRI, muscle strength testing and muscle biopsy analysis. Other clinical features were also recorded.RESULTS: Presenting symptoms were difficulties in walking, pain during exercise, delayed motor milestones and learning disabilities at school. All had some degree of cognitive impairment. Brain MRIs were abnormal in 3 of 10 patients, showing ventricular enlargement in one, periventricular hyperintensities in another and frontal atrophy of the left hemisphere in a third patient. Most affected muscle groups were hip and knee flexors and extensors on strength testing. On MRI, most affected muscles were hamstrings followed by paraspinal and gluteal muscles. The 12 patients in our cohort carried 11 alleles with known mutations, whereas 11 novel mutations accounted for the remaining 13 alleles.CONCLUSION: We describe the first cohort of patients with LGMD2N and show that unlike other LGMD types, all patients had cognitive impairment. Primary muscle involvement was found in hamstring, paraspinal and gluteal muscles on MRI, which correlated well with reduced muscle strength in hip and knee flexors and extensors. The study expands the mutational spectrum for LGMD2N, with the description of 11 novel POMT2 mutations in the association with LGMD2N.CLINICAL TRIAL REGISTRATION: NCT02759302.

U2 - 10.1136/jnnp-2017-317018

DO - 10.1136/jnnp-2017-317018

M3 - Journal article

C2 - 29175898

SN - 0022-3050

VL - 89

SP - 506

EP - 512

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

IS - 5

ER -

Limb girdle muscular dystrophy due to mutations in POMT2

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