Comparative analysis of features phenotype limb-girdle muscular dystrophy 2А and 2I types

A comparative analysis of the frequency of occurrence of 36 clinical symptoms in the three groups of patients with LGMD 2A and LGMD 2I
types and LGMD those patients who have mutations in CAPN3 and FKRP was detected. The absence of a particular symptom, allowing for the
differentiation of these genetic variants on clinical level. An algorithm for molecular genetic investigation of patients according to age at onset and some clinical symptoms. The proposed algorithm can significantly reduce the economic and time costs during expensive standing DNA analysis.

1. Zatz M., de Paula F., Starling A., Vainzof M. The 10 autosomal recessive limbgirdle muscular dystrophies. Neuromuscul Disord 2003;13:532–44.

2. http: // www.ncbi.nlm.nih.gov.

3. Richard I., Broux O., Allamand V. et al. Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A. Cell 1995;81:27–40.

4. Urtasun M., Saenz A., Roudaut C. et al. Limbgirdle muscular dystrophy in Guipuzcoa (Basque Country, Spain). Brain 1998;121:1735–47.

5. de Paula F., Vainzof M., Passos-Bueno M.R. et al. Clinical variability in Calpainopathy − what makes the difference? Eur J Hum Genet 2002;10:825–32.

6. Рыжкова О.П., Билева Д.С., Дадали Е.Л. и др. Клинико-генетические характеристики поясно-конечностной прогрессирующей мышечной дистрофии 2А типа. Мед генетика 2010;9(11):3–10.

7. Mercuri E., Sewry C.A., Brown S.C. et al. Congenital muscular dystrophy with secondary merosin deficiency and normal brain MRI: a novel entity. Neuropediatrics 2000;31:186–9.

8. Brockington M., Yuva Y., Prandini P. et al. Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C. Hum Molec Genet 2001;10:2851–9.

9. Driss A., Amouri C., Hamida C.B. et al. A new locus for autosomal recessive limb girdle muscular dystrophy in a large consanguineous Tunisian family maps to chromosome 19q13.3. Neuromusc Disord 2000;10:240–6.

10. Hanisch F., Grimm D., Zierz S., Deschauer M. Frequency of the FKRP mutation c.826C>A in isolated hyperCKemia and in limb girdle muscular dystrophy type 2 in German patients. J Neurol 2010;257(2):300–1.

11. Рыжкова О.П., Шаркова И.В., Дадали Е.Л. и др.Клинико-генетический анализ поясно-конечностной мышечной дистрофии 2I типа. Журн неврол и психиатр 2012;(6):55–9.

12. Passos-Bueno M.R., Moreira E.S., Marie S.K. et al. Main clinical features of the three mapped autosomal recessive limb-girdle muscular dystrophies and es - timated proportion of each form in 13 Brazilian families. J Med Genet 1996;33:97–102.

13. Fanin M., Duggan D.J., Mostacciuolo M.L. et al. Genetic epidemiology of muscular dystrophies resulting from sarcoglycan gene mutations. J Med Genet 1997;34:973–7.

14. Vainzof M., Passos-Bueno M.R., Pavanello R.C. et al. Sarcoglycanopathies are responsible for 68 % of severe autosomal recessive limb-girdle muscular dystrophy in the Brazilian population. J Neurol Sci 1999;164:44–9.

15. Udd B., Kaarianen H., Somer H. Muscular dystrophy with separate clinical phenotypes in a large family. Muscle Nerve 1991;14:1050–8.

16. Frosk P., Del Bigio M.R., Wrogemann K., Greenberg C.R. Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I. Europ J Hum Genet 2005;13:978–82.

17. Jarry J., Rioux M.F., Bolduc V. et al. A novel autosomal recessive limb-girdle muscular dystrophy with quadriceps atrophy maps to 11p13-p12. Brain 2007;130:368–80.

18. Boito C.A., Melacini P., Vianello A. et al. Clinical and molecular characterization of patients with limb-girdle muscular dystrophy type 2I. Arch Neurol 2005;62:1894–9.

19. Fanin M., Nascimbeni A.C., Fulizio L. et al. Loss of calpain-3 autocatalytic activ - ity in LGMD2А patients with normal protein expression. Am J Pathol 2003;163:1929–36.

20. Fanin M., Nascimbeni A.C., Angelini C. Screening of calpain-3 autolytic activity in LGMD muscle.– a functional map of CAPN3 gene mutations. J Med Genet 2007;44:38–43.

21. Talim B., Ognibene A., Mattioli E. et al. Normal calpain expression in genet - ically confirmed limb-girdle muscular dystrophy type 2A. Neurology 2001;56:692–3.

22. Yamamoto L.U., Velloso F.J., Lima B.L. et al. Muscle protein alterations in LGMD2I patients with different mutations in the Fukutin-related protein gene. J Histochem Cytochem 2008;56:995–1001.

23. Дадали Е.Л., Щагина О.А., Тибуркова Т.Б. и др. Особенности клинических проявлений и алгоритмы молекулярно-генетической диагностики генетически гетерогенных вариантов наследственных прогрессирующих мышечных дистрофий. В сб.: Молекулярно-биологические технологии в медицинской практике. Под ред. А.Б. Масленникова. Новосибирск: Арт-Лайн, 2010. Вып. 14. С. 174–183.

24. Рыжкова О.П., Дадали Е.Л., Щагина О.А. и др. Алгоритмы клинико- молекулярно-генетической диагностики наследственных прогрессирующих мышечных дистрофий. Мед генетика 2011;2:17–23.