@article {Nguyen590, author = {Karine Nguyen and Natacha Broucqsault and Charlene Chaix and Stephane Roche and J{\'e}r{\^o}me D Robin and Catherine Vovan and Laurene Gerard and Andr{\'e} M{\'e}garban{\'e} and Jon Andoni Urtizberea and Remi Bellance and Christine Barn{\'e}rias and Albert David and Bruno Eymard and Melanie Fradin and V{\'e}ronique Manel and Sabrina Sacconi and Vincent Tiffreau and Fabien Zagnoli and Jean-Marie Cuisset and Emmanuelle Salort-Campana and Shahram Attarian and Rafa{\"e}lle Bernard and Nicolas L{\'e}vy and Frederique Magdinier}, title = {Deciphering the complexity of the 4q and 10q subtelomeres by molecular combing in healthy individuals and patients with facioscapulohumeral dystrophy}, volume = {56}, number = {9}, pages = {590--601}, year = {2019}, doi = {10.1136/jmedgenet-2018-105949}, publisher = {BMJ Publishing Group Ltd}, abstract = {Background Subtelomeres are variable regions between telomeres and chromosomal-specific regions. One of the most studied pathologies linked to subtelomeric imbalance is facioscapulohumeral dystrophy (FSHD). In most cases, this disease involves shortening of an array of D4Z4 macrosatellite elements at the 4q35 locus. The disease also segregates with a specific A-type haplotype containing a degenerated polyadenylation signal distal to the last repeat followed by a repetitive array of β-satellite elements. This classification applies to most patients with FSHD. A subset of patients called FSHD2 escapes this definition and carries a mutation in the SMCHD1 gene. We also recently described patients carrying a complex rearrangement consisting of a cis-duplication of the distal 4q35 locus identified by molecular combing.Methods Using this high-resolution technology, we further investigated the organisation of the 4q35 region linked to the disease and the 10q26 locus presenting with 98\% of homology in controls and patients.Results Our analyses reveal a broad variability in size of the different elements composing these loci highlighting the complexity of these subtelomeres and the difficulty for genomic assembly. Out of the 1029 DNA samples analysed in our centre in the last 7 years, we also identified 54 cases clinically diagnosed with FSHD carrying complex genotypes. This includes mosaic patients, patients with deletions of the proximal 4q region and 23 cases with an atypical chromosome 10 pattern, infrequently found in the control population and never reported before.Conclusion Overall, this work underlines the complexity of these loci challenging the diagnosis and genetic counselling for this disease.}, issn = {0022-2593}, URL = {https://jmg.bmj.com/content/56/9/590}, eprint = {https://jmg.bmj.com/content/56/9/590.full.pdf}, journal = {Journal of Medical Genetics} }