• Clinical research of phenotype-genotype relationships for chromosome abnormalities, especially those detected prenatally

Trisomy is extremely frequent in humans at conception, affecting about 4% of clinically recognized pregnancies.  Most trisomic conceptuses are lost in the first trimester.  However, some trisomic pregnancies proceed to term, and one of the mechanisms thought to play a role is chromosome mosaicism.  Because the distribution of the trisomic cell line typically appears random, and the clinical consequences vary from case to case, a prenatal finding of mosaicism raises counselling issues.  By extensively studying cases of fetal trisomy mosaicism and reviewing the literature, we will determine whether patterns of distribution can be found that will enhance the understanding of and counselling for cases of prenatally detected trisomy mosaicism.

Sex chromosome abnormalities occur in approximately 0.2% of live births.  Common sex chromosome anomalies such as 45,X, 47,XXY, 47,XXX, and 47,XYY are well described and associated for the most part with predictable phenotypes.  However, rare sex chromosome abnormalities often are limited to individual case reports, raising the possibility of inaccurate phenotype prediction due to biased ascertainment.  An isodicentric chromosome for the short arm of the Y chromosome (idic Yp) is associated with a wide range of phenotypes in postnatally ascertained cases.  It has been reported in females with either Turner syndrome or with short stature alone, children with ambiguous genitalia, boys with mental retardation and craniofacial abnormalities or short stature and incomplete masculinization, a male with short stature and schizophrenia, infertile men with short stature, and phenotypically normal males with infertility.  Reports of prenatally diagnosed cases of idic Yp are rare and have limited patient follow-up.  We plan to present the prenatal cytogenetic findings and postnatal outcomes of a series of idic Yp cases, to review the literature, and to provide recommendations for cytogenetic analysis and counselling.

H Bruyere, MD Speeyak, E Winsor, B de Freminville, SA Farrell, J McGowan-Jordan, B McGillivray, D Chitayat, D McFadden, V Adouard, D Terespolsky, F Prieur, T Pantzar, M Hrynchak. 2005. Isodicentric Yp: prenatal diagnosis and outcome in eleven cases.  Submitted to Prenatal Diagnosis.

JL Gair, L Arbour, R Rupps, H Bruyere, WP Robinson. Recurrent Trisomy 21: Four Cases in Three Generations. Clinical Genetics. In press.

H Bruyere, RD Wilson, S Langlois.  2004.  Risk of mosaicism and uniparental disomy associated with the prenatal diagnosis of non-homologous Robertsonian translocation carrier. Fetal Diagn Ther. Sep-Oct; 19(5):399-403.  Review.

H Bruyere, E Separovic, J Doyle, T Pantzar, S Langlois. 2003. Familial cryptic terminal translocation (2; 17) ascertained through recurrent spontaneous abortions. Am J Med Genet. Dec 15; 123(3):285-9.

S Ma, SS Tang, BH Yuen, H Bruyere, M Penaherrera, Robinson WP. 2003. Cytogenetic and molecular study of a premature male infant with 46,XX derived from ICSI: case report. Hum Reprod. Nov; 18(11):2298-301.

WP Robinson, DE McFadden, IJ Barrett, B Kuchinka, MS Penaherrara, H Bruyere, RG Best, DAL Pedreira, S Langlois, DK Kalousek. 2002. Origin of amnion and implications for evaluation of the fetal genotype in cases of mosaicism.  Prenat Dian 22:1078-87.

P Stromme, ME Mangelsdorf, MA Shaw, KM Lower, SMS Lewis, H Bruyere, AK Gedeon, IE Scheffere, G Turner, M Partington, S Frints, J-P Fryns, GR Sutherland, JC Mulley, J Gecz. 2001.  Mutations of the human ortholog of Aristaless cause X-linked mental retardation and epilepsy. Nature Genetics. Apr; 30(4):441-5.

MS Penaherrera, IJ Barrett, CJ Brown, S Langlois, SL Yong, S Lewis, H Bruyere, PN Howard-Peeble, DK Kalousek, WP Robinson. 2000.  An association between skewed X-chromosome inactivation and abnormal outcome in mosaic trisomy 16 confined predominantly to the placenta. Clin Genet. Dec; 58(6):436-46.

H Bruyere, R Rupps, BD Kuchinka, JM Friedman, WP Robinson. 2000. Recurrent trisomy 21 in a couple with a child presenting trisomy 21 mosaicism and maternal uniparental disomy for chromosome 21 in the euploid cell line. Am J Med Genet. 94(1):35-41.

H Bruyere, SMS Lewis, S Wood, PJ McLeod, S Langlois. 2000. Confirmation of linkage of X-linked infantile spasms (West syndrome) and refinement of disease locus to Xp21.3-Xp22.1. Search on epilepsy. 7(2):21-23.