Group Wallgren-Pettersson & Pelin

Nemaline Myopathy and Related Disorders

Our aims are to identify the genetic causes of the nemaline myopathies (NM) and related disorders, elucidate the pathogenetic mechanisms, develop diagnostic methods, and work towards therapeutic trials. One focus is on the nebulin gene. We have established mutational and clinical databases on NM.

Our longstanding work on the genes for NM has resulted in a set of diagnostic methods, which we are developing further for more complete coverage of the causative genes using custom-made microarrays, exome sequencing, nanopore sequencing technology, and functional studies for the assessment of the pathogenicity of missense mutations. Therefore, our group is often contacted by colleagues around the world for help, especially regarding diagnosis of nebulin-caused NM. Assistance is requested with interpreting exome sequencing results, especially the significance of missense mutations, finding a second mutation in the nebulin gene in patients where only one such mutation has been identified, interpreting the clinical correlates of mutations identified, or a combination of these queries. A further result of our novel methodological developments, through our custom-made array for the hitherto known genes for NM, is the identification of novel mutational mechanisms in the genes previously known to cause NM. Furthermore, we have identified two novel genes likely to cause NM, and are studying these genes and their protein products further in collaboration with international groups.

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Post-Doctoral Scientist

Vilma-Lotta Lehtokari, PhD

Affiliated Senior Scientists

Kirsi Kiiski, PhD

Mikaela Grönholm, PhD, Docent

Graduate Students

Jenni Laitila, MSc

Lydia Sagath, MSc

Johanna Lehtonen

Undergraduate Students

Sampo Koivunen

Staff

Marilotta Turunen, Research Assistant

1. Pelin K, Hilpelä P, Sewry C , Akkari PA, Wilton SD, Wattanasirichaigoon D, Bang M-L, Centner T, Hanefeld F, Odent S, Fardeau M, Urtizberea JA, Muntoni F, Dubowitz V, Beggs AH, Laing NG, Labeit S, de la Chapelle A, Wallgren-Pettersson C. Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Proc. Natl. Acad. Sci. USA 1999;96:2305-2310.

2. Donner K, Ollikainen M, Ridanpää M, Christen H-J, Goebel HH, de Visser M, Pelin K, Wallgren Pettersson C: Mutations in the -tropomyosin (TPM2) gene – a rare cause of nemaline myopathy. Neuromuscul. Disord. 2002;12:151-158.

3.Donner K, Sandbacka M, Lehtokari V-L, Wallgren-Pettersson C, Pelin K: Complete genomic structure of the human nebulin gene and identification of alternatively spliced isoforms. Eur. J. Hum. Genet. 2004;12:744-51.

4. Wallgren-Pettersson C, Lehtokari V-L, Kalimo H, Paetau A, Hackman P, Sewry C, Pelin K, Udd B: Autosomal recessive distal myopathy caused by missense mutations in the nebulin gene. Brain 2007;130:1465-1476.

5. Lehtokari V-L*, Greenleaf RS*, DeChene ET, Kellinsalmi M, Pelin K, Laing NG, Beggs AH, Wallgren-Pettersson C: The exon 55 deletion in the nebulin gene – one single founder mutation with world-wide occurrence. Neuromuscul. Disord. 2009;19:179-181. * författarnas andel likvärdig

6. Laitila J*, Hanif M*, Paetau A, Hujanen S, Keto J, Somervuo P, Huovinen S, Udd B, Wallgren-Pettersson C, Auvinen P, Hackman P, Pelin K: Expression of multiple nebulin isoforms in human brain. Muscle & Nerve 2012;46:730-737. * författarnas andel likvärdig

7. Kiiski K, Laari L, Lehtokari V-L, Lunkka-Hytönen M, Angelini C, Petty R, Hackman P, Wallgren-Pettersson C, Pelin K: Targeted array CGH – a new diagnostic tool for the detection of large copy number variations in nemaline myopathy-causing genes. Neuromuscul. Disord. 2013;23:56-65.

8. Marttila M, Lehtokari V-L, Marston, S, Nyman TA, Barnerias C, Beggs AH, Bertini E, Ceyhan-Birsoy Ö, Cintas P, Gerard M, Gilbert-Dussardier B, Hogue JS, Longman C, Eymard B, Frydman M, Kang PB, Klinge L, Kolski H, Lochmüller H, Magy L, Manel V, Mayer M, Mercuri E, Taratuto A, de Visser M, Wilichowski E, Winer JB, Nowak K, Laing NG, Winder TL, Monnier N, Clarke NF, Pelin K, Grönholm M, Wallgren-Pettersson C: Genotype-phenotype correlations for novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies. Human Mutation 2014;35:779-90.

9. Lehtokari V-L, Kiiski K, Sandaradura SA, Laporte J, Repo P, Frey JA, Donner K, Marttila M, Saunders C, Barth PG, den Dunnen JT, Beggs A, Clarke NF, North KN, Laing, NG, Romero NB, Winder TL, Pelin K, Wallgren-Pettersson C: Mutation update: the spectrum of nebulin variants and associated myopathies. Human Mutat. 2014; 35:1418-1426.

10. Kiiski K, Lehtokari VL, Löytynoja A, Ahlstén L, Laitila J, Wallgren-Pettersson C, Pelin K: A recurrent copy number variation of the NEB triplicate region: only revealed by the targeted nemaline myopathy CGH array. EJHG doi: 10.1038/ejhg.2015a.166. [Epub ahead of print]

The Folkhälsan Research Foundation

The Finska Läkaresällskapet (Medical Society of Finland)

The Medicinska Understödsföreningen Liv och Hälsa (Life and Health Medical Fund)

The Sigrid Jusélius Foundation

Association Francaise contre les Myopathies

Muscular Dystrophy UK

The Oskar Öflund Foundation

The Otto Malm Foundation

The University of Helsinki

Professor Nigel G. Laing and Dr. Kristen Nowak, Perth, Australia

The International Consortium on Nemaline Myopathy

    • Carina Wallgren-Pettersson

      MD, PhD, Docent, Group Leader

    • phn:

    • Folkhälsan Research Center P.O. Box 63, FI-00014 University of Helsinki

    • Contact
    • Katarina Pelin

      PhD, Docent, Co-PI

    • phn:

    • Folkhälsan Research Center P.O. Box 63, FI-00014 University of Helsinki E-mail: katarina.pelin at helsinki.fi

    • Contact