Pure de-novo 5 Mb duplication at Xp11.22-p11.23 in a male:: phenotypic and molecular characterization

Males with duplications within the short arm of the X chromosome are rare and most cases are inherited from a maternal heterozygote. Here we describe the first detailed characterization of a de-novo Xp duplication delineated to Xp11.22 -> Xp11.23 in a 15-year-old male with moderate mental impairment, autistic-like behaviour, short stature, and mild dysmorphic features. Chromosome analysis (550 band resolution) was normal and comparative genomic hybridization (CGH) analysis on metaphase spreads detected duplication on Xp11. Further characterization of the duplication by array CGH, FISH experiments with specific BAC probes, and genotyping with microsatellite markers helped to determine proximal and distal breakpoints giving a size of the duplication of approximately 5Mb. As far as we are aware this is the first described male with isolated microduplication on Xp11.22-Xp11.23. Among the genes included within the duplicated region, and particularly those which are outside copy number polymorphisms, we discuss the relationship of FTSJ1, PQBP1 and HDAC6 with the clinical symptoms of our patient.