ABSTRACT
Thirty-two patients with fertility problems were identified as carriers of small supernumerary marker chromosomes (sSMC). Molecular cytogenetic techniques were used to characterize their chromosomal origin. Together with the other cases available in the literature 111 sSMC cases have now been detected in connection with fertility problems in otherwise clinically healthy persons and characterized for their genetic content. According to this study, in 60% of the cases the sSMC originated from chromosomes 14 or 15. Euchromatic imbalances were caused by the sSMC presence in 30% of the cases. Notably, in 53% of infertile sSMC carriers, the sSMC was parentally transmitted. As we found indications of an as yet unknown mechanism for the elimination of sSMC from the human gene pool, sSMC could also play a role in elucidating the process of chromosome gain and loss during evolution. Nonetheless, further detailed molecular analysis will be necessary in the future to characterize the mechanisms and genetic basis for this phenomenon.
Subject(s)
Chromosome Aberrations , Cytogenetic Analysis/methods , Infertility/genetics , Abortion, Habitual/genetics , Adult , Amenorrhea/genetics , Chromosome Banding , Chromosome Painting , Chromosomes, Human, Pair 14/genetics , Chromosomes, Human, Pair 15/genetics , Euchromatin/genetics , Evolution, Molecular , Female , Genetic Variation , Genotype , Humans , Infertility, Female/genetics , Infertility, Male/genetics , Karyotyping , Male , Phenotype , Review Literature as TopicABSTRACT
A boy with severe mental retardation, funnel chest, bell-shaped thorax, and hexadactyly of both feet was found to have a balanced de novo t(12;17)(p13.3;q21.3) translocation. FISH with BAC clones and long-range PCR products assessed in the human genome sequence localized the breakpoint on chromosome 17q21.3 to a 21-kb segment that lies <30 kb upstream of the HOXB gene cluster and immediately adjacent to the 3' end of the TTLL6 gene. The breakpoint on chromosome 12 occurred within telomeric hexamer repeats and, therefore, is not likely to affect gene function directly. We propose that juxtaposition of the HOXB cluster to a repetitive DNA domain and/or separation from required cis-regulatory elements gave rise to a position effect.
Subject(s)
Chromosomes, Human, Pair 12/genetics , Chromosomes, Human, Pair 17/genetics , Developmental Disabilities/genetics , Genes, Homeobox/genetics , Musculoskeletal Abnormalities/genetics , Translocation, Genetic , Child, Preschool , Chromosome Breakage , Chromosome Mapping , Humans , MaleABSTRACT
Proximal myotonic myopathy/myotonic dystrophy type 2 (PROMM/DM 2) is caused by an expansion of the (TG)n(TCTG)n(CCTG)n repeat tract in intron 1 of the ZNF9 gene located on chromosome 3q21. Because these expansions show a marked mitotic instability, expanded alleles are often difficult to detect. In order to improve the diagnostic procedure, we applied a combination of pulsed-field gel electrophoresis and semi-quantitative Southern blot analysis with a novel hybridization probe. The combination of these methods led to unequivocal results in about 98% of cases with a clinical diagnosis of PROMM/DM 2. Furthermore, we report the genotype/phenotype correlation in a patient lacking a normal ZNF9 allele and a further proband with a "grey zone" allele.
