Mild clinical presentation in KLHL40-related nemaline myopathy (NEM 8).

Child; Female; Humans; Muscle Proteins/genetics/metabolism; Muscle, Skeletal/metabolism/pathology; Mutation; Myopathies, Nemaline/genetics/pathology/physiopathology; Phenotype; KLHL40; Nemaline myopathy

Abstract :

[en] Nemaline myopathies are clinically and genetically heterogeneous muscle diseases characterized by the presence of nemaline bodies (rods) in muscle fibers. Mutations in the KLHL40 (kelch-like family member 40) gene (NEM 8) are common cause of severe/lethal nemaline myopathy. We report an 8-year-old girl born to consanguineous Moroccan parents, who presented with hypotonia and poor sucking at birth, delayed motor development, and further mild difficulties in walking and fatigability. A muscle biopsy revealed the presence of nemaline bodies. KLHL40 gene Sanger sequencing disclosed a never before reported pathogenic homozygous mutation which resulted in absent KLHL40 protein expression in the muscle. This further expands the phenotypical spectrum of KLHL40 related nemaline myopathy.

Disciplines :

Pediatrics

Author, co-author :

Seferian, Andreea M.

Malfatti, Edoardo

Bosson, Caroline

Pelletier, Laurent

Taytard, Jessica

Forin, Veronique

Gidaro, Teresa

Gargaun, Elena

Carlier, Pierre

Faure, Julien

More authors (3 more)

Language :

English

Title :

Mild clinical presentation in KLHL40-related nemaline myopathy (NEM 8).

Publication date :

2016

Journal title :

Neuromuscular Disorders

ISSN :

0960-8966

eISSN :

1873-2364

Publisher :

Elsevier, Netherlands

Volume :

Issue :

Pages :

712-716

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 18 February 2022

Statistics

Number of views

66 (0 by ULiège)

Number of downloads

90 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

[1] North, K.N., Laing, N.G., Wallgren-Pettersson, C., Nemaline myopathy: current concepts. The ENMC International Consortium and Nemaline Myopathy. J Med Genet 34 (1997), 705–713.
[2] Wallgren-Pettersson, C., Laing, N.G., Report of the 70th ENMC International Workshop: nemaline myopathy, 11–13 June 1999, Naarden, The Netherlands. Neuromuscul Disord 10 (2000), 299–306.
[3] Nowak, K.J., Wattanasirichaigoon, D., Goebel, H.H., et al. Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy. Nat Genet 23 (1999), 208–212.
[4] Agrawal, P.B., Greenleaf, R.S., Tomczak, K.K., et al. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. Am J Hum Genet 80 (2007), 162–167.
[5] Lehtokari, V.L., Pelin, K., Sandbacka, M., et al. Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Hum Mutat 27 (2006), 946–956.
[6] Johnston, J.J., Kelley, R.I., Crawford, T.O., et al. A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. Am J Hum Genet 67 (2000), 814–821.
[7] Donner, K., Ollikainen, M., Ridanpaa, M., et al. Mutations in the beta-tropomyosin (TPM2) gene – a rare cause of nemaline myopathy. Neuromuscul Disord 12 (2002), 151–158.
[8] Laing, N.G., Wilton, S.D., Akkari, P.A., et al. A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy NEM1. Nat Genet, 10, 1995, 249.
[9] Sambuughin, N., Swietnicki, W., Techtmann, S., et al. KBTBD13 interacts with Cullin 3 to form a functional ubiquitin ligase. Biochem Biophys Res Commun 421 (2012), 743–749.
[10] Ravenscroft, G., Miyatake, S., Lehtokari, V.L., et al. Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy. Am J Hum Genet 93 (2013), 6–18.
[11] Gupta, V.A., Ravenscroft, G., Shaheen, R., et al. Identification of KLHL41 Mutations Implicates BTB-Kelch-Mediated Ubiquitination as an Alternate Pathway to Myofibrillar Disruption in Nemaline Myopathy. Am J Hum Genet 93 (2013), 1108–1117.
[12] Yuen, M., Sandaradura, S.A., Dowling, J.J., et al. Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy. J Clin Invest 125 (2015), 456–457.
[13] Malfatti, E., Bohm, J., Lacene, E., Romero, N., Laporte, J., A premature stop codon in MYO18B is associated with severe nemaline myopathy with cardiomyopathy. Neuromuscul Disord, 25, 2015, S186.
[14] Prag, S., Adams, J.C., Molecular phylogeny of the kelch-repeat superfamily reveals an expansion of BTB/kelch proteins in animals. BMC Bioinformatics, 4, 2003, 42.
[15] Gong, W., Gohla, R.M., Bowlin, K.M., Koyano-Nakagawa, N., Garry, D.J., Shi, X., Kelch repeat and BTB domain containing protein 5 (Kbtbd5) regulates skeletal muscle myogenesis through the E2F1-DP1 complex. J Biol Chem 290 (2015), 15350–15361.
[16] Kawase, K., Nishino, I., Sugimoto, M., et al. Nemaline myopathy with KLHL40 mutation presenting as congenital totally locked-in state. Brain Dev 37 (2015), 887–890.
[17] Natera-de Benito, D., Nascimento, A., Abicht, A., et al. KLHL40-related nemaline myopathy with a sustained, positive response to treatment with acetylcholinesterase inhibitors. J Neurol 263 (2016), 517–523.
[18] Cheng, W.Y., Hakenberg, J., Li, S.D., Chen, R., DIVAS: a centralized genetic variant repository representing 150 000 individuals from multiple disease cohorts. Bioinformatics 32 (2016), 151–153.
[19] Li, M.X., Gui, H.S., Kwan, J.S., Bao, S.Y., Sham, P.C., A comprehensive framework for prioritizing variants in exome sequencing studies of Mendelian diseases. Nucleic Acids Res, 40, 2012, e53.
[20] Van Durme, J., Delgado, J., Stricher, F., Serrano, L., Schymkowitz, J., Rousseau, F., A graphical interface for the FoldX forcefield. Bioinformatics 27 (2011), 1711–1712.
[21] Jungbluth, H., Sewry, C.A., Counsell, S., et al. Magnetic resonance imaging of muscle in nemaline myopathy. Neuromuscul Disord 14 (2004), 779–784.