Abstract
We describe a family in which the largest hitherto reported pericentric inversion of chromosome 18, inv(18)(p11.22q23), segregates. Individuals heterozygous for the nonrecombinant inversion were unaffected. However, those heterozygous for either the dup(18p)/del(18q) or dup(18q) /del(18p) recombinant exhibited mild learning difficulty, personality disorders and deficient social behavior in the absence of mental retardation. Of the three family members tested, the behavioral abnormalities were more prominent in the two individuals with the dup(18p)/del(18q) recombinant than in the one with the dup(18q)/del(18p) recombinant. Genetic counseling issues for this family, in particular for the affected, include the enhanced probability of reduced fertility as well as the recurrence risk of the parental inversion equaling 1/2 in surviving offspring. This observation kindles the interest in determining the frequency of subtelomeric rearrangements in individuals with learning difficulty and deficiency in social interaction, phenotypic features often considered to be of multifactorial causation.
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Acknowledgements
We thank The Wellcome Trust Sanger Institute (Hinxton, Cambridge, UK) for providing us with the BAC probes for chromosome 18. The YAC probe HTY3045 was kindly provided by Dr A Jauch, Laboratory of Human Genetics, Heidelberg, Germany. This study is supported by Research Grants from the Fund for Scientific Research – Flanders (Belgium): 1.5.183.02, G.0200.03 and the Interuniversitary Attraction Poles Programme – Belgian Science Policy initiated by the Belgian State, Prime Minister's Office. The senior author (JGL) is indebted to the Center of Medical Genetics (chairperson: Dr Anne De Paepe), Ghent University Hospital, Ghent, Belgium and to the Greenwood Genetic Center (director: Dr Roger E Stevenson), Greenwood, SC, USA for the accommodation and academic support.
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Supplementary Information accompanies the paper on European Journal of Human Genetics website (http://www.nature.com/ejhg).
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Vermeulen, S., Speleman, F., Vanransbeeck, L. et al. Familial pericentric inversion of chromosome 18: behavioral abnormalities in patients heterozygous for either the dup(18p)/del(18q) or dup(18q)/del(18p) recombinant chromosome. Eur J Hum Genet 13, 52–58 (2005). https://doi.org/10.1038/sj.ejhg.5201281
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DOI: https://doi.org/10.1038/sj.ejhg.5201281
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