Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females

Editor—Centromeres are the specialised regions of chromosomes that ensure normal transmission of sister chromatids to each daughter cell after mitosis. Alphoid satellite DNA sequences, consisting of tandemly repeated ≅170 bp units present at all human centromeres, contain the information necessary for centromeric function,1 despite the observation of marker chromosomes lacking detectable alphoid DNA.2-4 Dicentric chromosomes, resulting from some Robertsonian or Y;autosome translocations, represent a valuable tool for studying factors which ensure that only one of the centromeres is mitotically active, thus preventing chromosomal bridges and breakages to occur at anaphase. It has been shown that centromeric inactivation is largely an epigenetic event5 based on the ability of alphoid sequences to bind specific centromeric proteins (CENPs), particularly the CENP-C protein which is necessary for proper kinetochore assembly.6 Here we describe a de novo dicentric Y;13 (q12;p11) translocation chromosome found in a severely oligozoospermic patient and exhibiting a variable pattern of centromeric activity, as defined by the localisation of the primary constriction. This patient was a healthy, 20 year old, West Indian man who referred himself to the laboratory because of ejaculation problems. Sperm analysis showed first an abnormal viscosity of ejaculate which took as long as six hours to liquefy and, second, an extreme oligozoospermia at 0.1 million spermatozoa/ml. Biochemical parameters of the semen were normal. Further sperm counts showed a similar constitution of ejaculate and testicular impairment varying from severe oligozoospermia to azoospermia or cryptozoospermia. Testicular biopsy was not proposed. Karyotyping was performed on blood lymphocytes by conventional cytogenetic methods using R and G banding and BrdU incorporation after cell culture synchronisation. It showed an apparently balanced reciprocal translocation between the distal region of the Y chromosome long arm and the short arm of one chromosome 13. Paternal chromosomes were normal. Curiously, this abnormal …