Project Details
Projekt
Genome analyses in patients suffering from DMD or LGMD for detection of deep-intronic variants and novel pathomechanisms in known genes
Subject Area
Human Genetics
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 444748124
Muscular dystrophies (MDs) are a genetically heterogeneous group of neuromuscular disorders and hence, rare hereditary diseases with more than 100 known subtypes. The X-chromosomal muscular dystrophy type Duchenne/Becker (DMD/BMD) as well as certain autosomal recessive limb-girdle muscular dystrophies (e.g. LGMDR1 and LGMDR2), which are clinically barely distinguishable from DMD/BMD, represent the most common MD forms with incidences up to 1:3000 in the European population. Despite relatively high detection rates of more than 50 % by molecular testing, a comparatively high percentage of clinically well characterized patients remains with no mutations detected in the DMD gene and/or none or only a single heterozygous mutation in one of the recessive LGMD genes. Due to the size of the relevant genes, only coding and splicing regions are examined in genetic diagnostics so far. Therefore, it seems reasonable to assume that mainly intronic, regulatory or structural variants, which cannot be detected by standard methods, are the underlying cause in clinically distinct DMD/BMD/LGMD patients without genetic diagnosis. Genome sequencing and data analysis of the complete genomic sequence of the relevant genes (especially DMD, ANO5, CAPN3, DYSF and FKRP) as well as subsequent functional analyses of the detected variants should improve the genetic detection rate for these MD patients in order to provide the possibility of an appropriate (personalized) therapy.
DFG Programme
Research Grants
