Abstract
Rearrangements of chromosome 15q, including isodicentric 15 chromosomes and interstitial duplications and triplications, have been previously reported in association with autism spectrum disorders. We have identified two boys with exceptionally large der(15) chromosomes that are tricentric and contain four copies of the proximal long arm, including the Prader Willi/Angelman critical region, and leading to hexasomy of the involved segment. Biallelic inheritance of maternal alleles and methylation analysis indicate that the markers are maternally derived. Clinical assessment of the boys indicated severe cognitive impairment associated with marked delays in gross and fine motor skills. Social and language deficits were present in both, although the severity of the mental retardation precluded diagnosis of autism (both were considered to have pervasive developmental disorder-not otherwise specified). Neurologic manifestations included infantile spasms evolving into intractable early-onset myoclonic seizures, psychomotor regression, and profound diffuse hypotonia. These patients represent the most severe end of the spectrum of phenotypes associated with segmental aneuploidy for chromosome 15q11-q13.
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Acknowledgements
The authors are grateful to the patients and their families for participating in this study. We also thank Donna Bennett of the IDEAS support group for her support of our work. We thank David Ledbetter and Judy Fantes for genomic clones and mapping information, Mario Rochhi for the pCM15 clone, and Rhona Schreck, Alma Lopez-Singh, and Laura Espana for their invaluable assistance. This work was supported by the NIH Collaborative Programs in Autism Research (PO1 HD35470), the M.I.N.D. Institute, the F & F Foundation, and Nemours Biomedical Research.
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Mann, S.M., Wang, N.J., Liu, D.H. et al. Supernumerary tricentric derivative chromosome 15 in two boys with intractable epilepsy: another mechanism for partial hexasomy. Hum Genet 115, 104–111 (2004). https://doi.org/10.1007/s00439-004-1127-5
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DOI: https://doi.org/10.1007/s00439-004-1127-5