XXXX : An effective sequencing approach to establish a genetic and clinical diagnosis.

@entity1 @entity20053 @entity31044 @entity12269 @entity30262 @entity15439 @entity6391 @entity1274 @entity74 @entity24129 @entity394
UNASSIGNED: @entity15439 is an @entity74 characterized by @entity6391 , @entity1274 and, in some cases, @entity394 . The disorder is clinically and genetically heterogeneous and, to date, mutations in 11 genes have been described. This finding makes difficult to get a precise molecular diagnosis and offer @entity1 accurate genetic counselling. To overcome this problem and to increase our knowledge of the molecular basis of @entity15439 , we designed a targeted resequencing custom panel. In a first validation step a series of 16 Italian @entity1 with known molecular diagnosis were analysed and 31 out of 32 alleles were detected (97% of accuracy). After this step, 31 @entity1 without a molecular diagnosis were enrolled in the study. Three out of them with an uncertain Usher diagnosis were excluded. One causative allele was detected in 24 out 28 @entity1 (86%) while the presence of both causative alleles characterized 19 @entity1 out 28 (68%). Sixteen novel and 27 known alleles were found in the following genes: @entity24129 (50%), @entity30262 (7%), @entity31044 (11%), @entity20053 (7%) and @entity12269 (2%). Overall, on the 44 @entity1 the protocol was able to characterize 74 alleles out of 88 (84%). These results suggest that our panel is an effective approach for the genetic diagnosis of @entity15439 leading to: 1) an accurate molecular diagnosis, 2) better genetic counselling, 3) more precise molecular epidemiology data fundamental for future interventional plans.
