Genetic diagnosis of Italian LGMD patients by NGS technology

When a clinical diagnosis of Iimb-girdle muscular dystrophy (LGMD) is made, the patient may receive little information about prognosis, treatment and genetic counselling. The term LGMD, in fact, simply defines a progressive weakness that begins from the proximal Iimb muscles. But many genetic diseases of muscle have the same symptoms. These different diseases have different severity and mechanisms. A muscle biopsy and a sample of blood is usually taken, but after a few months in 40% of cases the causative gene remains unknown. This percentage is similar in Italy, England, Nederland, Germany, Spain and France, while in other countries the number of "orphan" LGMD may be also higher. The explanation is that the genetic cause of LGMD cannot be easily discovered by routine tests. Traditional tests have the big disadvantages that you must address your research on a single gene each time. So the present genetic testing is long, expensive and ineffective. New powerful approaches for DNA analysis, like next-generation sequencing (NGS) are going to revolutionize the field, with a single instrument that can analyze all the human genome many times. We propose a NGS-based protocol to discover the large majority of the “orphan” LGMD mutations.