Research News

Genetic breakthrough offers help for rare disease

2.0 from 1 vote
Tuesday, November 15, 2011

A research group at the Genetics, Molecular and Cellular Biology Institute (IGBMC)1 in Illkirch, headed by Jocelyn Laporte and Jean-Louis Mandel, identified a gene that causes a congenital myopathy if mutated, called autosomal recessive centronuclear myopathy.

This finding allows for better understanding of the common pathological mechanism of the different forms in this myopathy type. The identification of the responsible gene causing a disease is also the first, and indispensable, step to eventually establishing therapeutic strategies.

This discovery therefore permits the development of a precise diagnostic investigation for patients as well as a prenatal diagnostic tool for couples at high risk.

This work, published recently in the science journal, Nature Genetics, was carried out in the research centers IGBMC of the CNRS at the Inserm, and at the University Louis Pasteur. It was supported by contracts from the French National Research Agency and an AFM grant from Téléthon.

Centronuclear myopathies are part of the congenital myopathy family of diseases. They are characterized by an abnormal centralized position of the nuclei in muscular fibers, whereas the nuclei are normally found in the periphery. Individuals afflicted by these neuromuscular diseases show a premature general muscle weakness and have difficulties with walking.

Currently, these myopathies affect less than one person in 10,000 in France and are transmitted from generation to generation by three types: X chromosome-linked, autosomal recessive or dominant2.

For some years, several genes are known to cause other forms of centronuclear myopathies: the myotubularin mutation (MTM1) causing the X-linked form and the dynamin 2 mutation causing the autosomal dominant form.

The recessive form has been described for a long time, but due to the small numbers of individuals affected, no gene has been identified so far. For the same reason, positional cloning, the usual genetic procedure that is employed for gene identification, was difficult to use.

The researchers therefore looked for mutations in certain specific genes in patients afflicted by the recessive form of the disease. These genes, called candidates, were chosen because they encode proteins with similar functions as myotubularin and dynamin 2, which cause the X-linked form and the autosomal dominant form of the disease.

The researchers thus detected mutations in BIN 1, a gene coding for the protein amphiphysin 2, which is involved in internal cellular architecture, as well as membrane transport and compartmentalization.

Preliminary results suggest that the observed defects in the muscular fibres of patients could be caused by aberrant membrane remodeling. Moreover, one of the documented mutations inhibits the binding of the proteins amphiphysin 2 and dynamin 2.

These results have allowed the researchers to link the recessive and dominant form of these myopathies at the molecular level. At present, the research team of the IGBMC is striving to unravel the disease mechanism.

These results will finally allow patients to benefit from a precise genetic diagnostic tool. Risk couples, in which both partners carry the mutation, will now be able to fulfill their desire for having children without fearing to transmit the disease thanks to prenatal diagnostics.

Ultimately, the identification of the gene is fundamental to better understand the disease and the physiological dysfunctions, provoked by the genetic mutation, so as to establish therapeutic strategies.

1 Institut de Génétique et de Biologie Moléculaire et Cellulaire (mixed research unit CNRS/Inserm/Université Louis Pasteur – UMR7104/UMRS596)

2 In case of the autosomal recessive form: the child is only affected by the disease if it inherits of both parents the mutated gene version. In case of the autosomal dominant form: the child is affected by the disease if it inherits one mutated gene version of either parent. In case of the X-linked form: in general, only men are affected by the disease and only women transmit the disease.

Further information:

Mutations in amphiphysin 2 (BIN 1) disrupt interaction with dynamin 2, and cause autosomal recessive centronuclear myopathy – Anne-Sophie Nicot, Anne Toussaint, Valérie Tosch, Christine Kretz, Carina Wallgren-Pettersson, Erik Iwarsson, Helen Kingston, Jean-Marie Garnier, Valérie Biancalana, Anders Oldfors, Jean-Louis Mandel, Jocelyn Laporte. Nature Genetics.

About the disease:

Association Française contre les Myopathies

0 810 811 088

Contact (researcher):

Jocelyn Laporte

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)

03 88 65 34 12

Contact (media):


Estelle Assaf, Delphine Carvalho

01 69 47 28 28


Priscilla Dacher

01 44 96 46 06


Séverine Ciancia

01 44 23 60 86

Université Louis Pasteur

Isabel Pellon

03 90 24 12 54

Author: Daniel Marks
Source: CheckOrphan
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