Severe mental retardation in six generations of a large South African family carrying a translocation t(6;10)(q27;q25·2)

Partial monosomy 10q25.2→qter, detected in a newborn baby with multiple congenital abnormalities, was found to be derived from a balanced maternal translocation t(6;10)(q27;q25.2). The pedigree of six generations of the family is presented. In an extensive cytogenetic study of this family, the chromosome complements of 57 subjects, potentially capable of carrying some form of this translocation, were analysed. A total of 14 male carriers (four obligatory) and 14 female carriers (three obligatory) of this translocation was found. Partial trisomy 10q25.2→qter, associated with severe mental retardation, occurred in nine cases, eight males and one female. Two of these eight males were detected prenatally and subsequently therapeutically aborted. The phenotypes of the family members with partial trisomy 10q25.2→qter are compared to each other and to those reported in publications. No further cases of partial monosomy 10q25.2→qter were encountered. A review of published reports of partial monosomy and partial trisomy 10qter is given. The apparent absence of infertility, the occurrence of many first trimester miscarriages, and the marked sex ratio are discussed.Articl

Fluorescent in situ hybridization evaluation of human Y-bearing spermatozoa separated by albumin density gradients

Objective: Fluorescent in situ hybridization of decondensed sperm nuclei was employed to evaluate the effectiveness of the Ericsson albumin gradient enrichment technique of Y-bearing sperm. Design: Mature human spermatozoa were separated from donor- and randomly selected patient semen using three different albumin density layers. Sperm nuclei, in the albumin layer with highest density, were decondensed and the percentage Y-bearing sperm was determined by fluorescent in situ hybridization. Results: A slight, although statistically significant, increase in percentage Y bearing sperm was observed. Conclusion: Although statistically significant, the clinical relevance of the small increase in Y-bearing sperm remains uncertain. A randomized controlled clinical study should help to clarify the above laboratory results.Articl

Deletion mapping of 39 random isolated Y-chromosome DNA fragments

Thirty-nine recombinants isolated from a Y chromosome-specific library were deletion mapped. Seven deletion intervals were defined by hybridization of probes to DNA of eight individuals with aberrant Y chromosomes. Extreme cytogenetic limits of the deletion intervals were determined by in situ hybridization of one probe per deletion interval. Five intervals, with a total of twenty-five probes, were allocated to the long-arm euchromatic region. The probes described will be useful for characterization of aberrant Y chromosomes, in searching for expressed sequences on the Y chromosome, and for further study of the evolutionary relationship between the Y chromosome and other chromosomes.Articl

A study of meningiomas in South Africa: Investigating a correlation between clinical presentation, histopathology and genetic markers

Objective. To determine whether there are certain genetic markers which correlate with particular clinical characteristics of meningiomas including multiplicity, recurrence and calvarial erosion. Methods. Thirty-eight South African-born patients with meningiomas were recruited for this study. At surgery, blood and tumour specimens were obtained for histopathological, cytogenetic and molecular analysis. Loss of heterozygosity (LOH) on chromosomes 1p and 22q were investigated and the NF2 gene on 22q12.2 was screened for disease-causing mutations. Results. The commonest tumour locations were convexity (25%) and parasagittal (21%). The histology results showed that 86.8% of the patients had Grade I tumours and the remainder had Grade II tumours. A pathogenic nonsense mutation, R341X in the NF2 gene was found in only one patient. LOH on each of chromosomes 1p and 22q was observed in 44.7% of patients, but in different individuals. Significant associations were found between having specific tumour characteristics and both male gender (p-value = 0.0059) and 22q LOH (p-value = 0.0425). We estimated that having 22q LOH makes an individual approximately four times more likely to develop a tumour that exhibits multiplicity, recurrence or calvarial erosion (OR = 4.8; 95% CI: 1.2-23.4). Adjusting for gender strengthened this effect (OR = 6.1; 95% CI: 1.1-48.7). Conclusions. Our data indicate that male patients and patients with a meningioma that has 22q LOH are more likely to develop tumours exhibiting multiplicity, recurrence or calvarial erosion. We recommend that this subset of patients should be followed up more closely. Further study is needed to determine the benefit of adjuvant radiation therapy in this scenario. © The Neurosurgical Foundation.Articl

Balanced chromosome translocations and abnormal phenotypes. A report of 5 cases

CITATION: Van Heerden, K.M.M. et al. 1986. Balanced chromosome translocations and abnormal phenotypes. A report of 5 cases. S Afr Med J, 69(6):825-828.The original publication is available at http://www.samj.org.zaENGLISH ABSTRACT: Five cases in which phenotypic abnormalities were found in association with apparent balanced chromosomal translocations are described. In 3 patients, one of the parents was found to be carrier of the same translocation. In a further patient, the translocation was shown to be de novo and in the remaining patient the father was not available for chromosome studies. In a review of the literature the breakpoints in 36 familial balanced translocations were compared with 40 de novo translocations (including the present cases) all associated with phenotypic abnormalities. No common translocation was found in these groups, but it was observed that chromosomes 4 and 5 were significantly more involved in de novo translocations than in familial translocations. The possible aetiology and implications for prenatal diagnosis are discussed.AFRIKAANSE OPSOMMING: Geen opsomming beskikbaarPublisher’s versio