RT Journal Article SR Electronic T1 Deciphering the complexity of the 4q and 10q subtelomeres by molecular combing in healthy individuals and patients with facioscapulohumeral dystrophy JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 590 OP 601 DO 10.1136/jmedgenet-2018-105949 VO 56 IS 9 A1 Karine Nguyen A1 Natacha Broucqsault A1 Charlene Chaix A1 Stephane Roche A1 Jérôme D Robin A1 Catherine Vovan A1 Laurene Gerard A1 André Mégarbané A1 Jon Andoni Urtizberea A1 Remi Bellance A1 Christine Barnérias A1 Albert David A1 Bruno Eymard A1 Melanie Fradin A1 Véronique Manel A1 Sabrina Sacconi A1 Vincent Tiffreau A1 Fabien Zagnoli A1 Jean-Marie Cuisset A1 Emmanuelle Salort-Campana A1 Shahram Attarian A1 Rafaëlle Bernard A1 Nicolas Lévy A1 Frederique Magdinier YR 2019 UL http://jmg.bmj.com/content/56/9/590.abstract AB 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.