A family with fragile X syndrome, Duchenne muscular dystrophy and ichthyosis transmitted by an asymptomatic carrier

• Published in: Clinical genetics 2014-03, Vol.85 (3), p.286-289
• Main Authors: Todorova, A., Litvinenko, I., Todorov, T., Tincheva, R., Avdjieva, D., Tincheva, S., Mitev, V.
• Format: Article
• Language: English
• Subjects: Adult; Becker's muscular dystrophy; Child; Chromosomes; DMD gene; DNA Methylation; Female; FMR1 gene; Fragile X Mental Retardation Protein - genetics; Fragile X Syndrome - genetics; Genetic linkage; Genetics; genomic instability; Genomics; Haplotypes; Heterozygote; Humans; Ichthyosis - genetics; Inheritance Patterns; Male; Muscular dystrophy; Muscular Dystrophy, Duchenne - genetics; Mutation; Proteins - genetics; recombination; Steryl-Sulfatase - genetics; STS gene; Trinucleotide Repeat Expansion
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.12148

The human X chromosome carries regions prone to genomic instability: deletions in the Xp22.31 region, involving the steroid sulfatase gene (STS) cause X‐linked ichthyosis; rearrangements in the Xp21.2 region are associated with Duchenne or Becker muscular dystrophies (DMD or BMD); and the Xq27.3 unstable region, containing the (CGG)n repeat expansion in the FMR1 gene is associated with fragile X syndrome. We report on a family with two affected boys, the elder diagnosed with fragile X syndrome, the younger with DMD, and both suffering from severe ichthyosis. The family was analyzed by polymerase chain reaction, multiplex ligation‐dependent probe amplification and haplotype analysis. The mother proved to be an asymptomatic carrier of all three non‐contiguous mutation events, involving the STS gene, the DMD gene and a FMR1 expansion. To the best of our knowledge, this is the first description of an asymptomatic carrier of three different X‐linked disorders, involving severe genetic rearrangements on both long and short arms of the X chromosomes. The boy with fragile X syndrome has inherited a triple recombinant maternal X chromosome, this way inheriting the FMR1 expansion and ichthyosis, originating most probably from different maternal Xes and excluding the DMD gene deletion. The transmission of these extremely defective maternal chromosomes to the next generation involved several recombinations.