Distal Xq disomy in males results in characteristic phenotypes that typically include mental retardation, microcephaly, prominent hypotonia and hypogonadism. The 8-year-old male patient reported here presented with mental retardation, prominent ears, abnormally wide and unstable gait and flat occiput. He did not have microcephaly or hypogonadism. Subtelomeric multi-fluorescence in-situ hybridization analysis identified a duplicated terminal portion of chromosome Xq/Yq located distally on Yp. Further analysis of the duplicated region using additional FISH probes, specific for the distal Xq and Yp chromosomal regions, and array comparative genomic hybridization analysis using the 244 K oligo-array of Agilent, showed that it spans approximately 2.15 Mb of the terminal Xq region and includes MECP2 but not L1CAM gene. This is the smallest well-characterized terminal Xq duplication reported to date. Genes proximal to MECP2 that are not duplicated in our patient are likely responsible for additional clinical manifestations including characteristic facial dysmorphic features, microcephaly, hypogonadism and more severe hypotonia, as noted in patients with larger distal Xq duplications. Our patient's features are similar to previously reported MECP2 gene duplication cases, thus suggesting minor or no contribution of duplicated genes distal of MECP2 to the reported phenotype.
aDepartment of Human Genetics, New York State Institute for Basic Research, Staten Island
bDepartment of Genetics and Genomic Sciences, The Mount Sinai School of Medicine, New York, New York, USA
cOspedale Casa Sollievo della Sofferenza, San Giovanni Rotondo e Instituto CSS-Mendel, Rome, Italy
Correspondence to Dr Milen Velinov, MD, PhD, Department of Human Genetics, NYS Institute for Basic Research, in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
Tel: +1 718 494 5219; fax: +1 718 494 1072;
Received 29 January 2008 Accepted 15 August 2008