True hermaphroditism associated with microphthalmia.
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A 4-year-old boy with an undescending left testis, penoscrotal hypospadia and bilateral microphthalmia was admitted to our hospital. Chromosome analysis revealed a karyotype of 46, XX del(x)(p2 2,31) and the sex-determining region of the Y chromosome (SRY) was negative. The right testis was located in the scrotum and a left cystic ovary-like gonad, a salpinx and a unicorn uterus were found in the left inguinal canal. Histologically the gonad was an ovotestis in which primordial follicles covered infantile seminiferous tubules. Microphthalmia is observed in some congenital syndromes caused by interstitial deletion of the X chromosome. This case suggested that the short arm of the X chromosome was involved in the differentiation of the gonad. Very closely located follicles and infantile seminiferous tubules indicated that induction of meiosis in the fetus was controlled by the local microenvironment in follicles and seminiferous tubules, and not by the systemic hormonal condition. (+info)
Triple X female and Turner's syndrome offspring.
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A mentally retarded young female having 47 chromosomes with a triple X karotype produced a child with Turner's syndrome associated with mental defeciency. To our knowledge this is the first example of a triple X female giving birth to a child with Turner's syndrome. (+info)
Asynchronous replication of alleles in genomes carrying an extra autosome.
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Transcriptional activity of genes appears to be highly related to their replication timing; alleles showing the common biallelic mode of expression replicate highly synchronously, whereas those with a monoallelic mode of expression replicate asynchronously. Here we used FISH to determine the level of synchronisation in replication timing of alleles in amniotic fluid cells derived from normal foetuses and from those with either of the trisomies for autosomes 21, 18 or 13, or for sex chromosomes (47,XXX and 47,XXY). Two pairs of alleles, not associated with the extra chromosome, were studied in subjects with each trisomy and three in normal subjects. In cells derived from normal foetuses and from foetuses with sex chromosome trisomies, each pair of alleles replicated synchronously; yet these very same alleles replicated asynchronously in cells derived from foetuses with trisomy for any of the three autosomes studied. The results suggest that the gross phenotypic abnormalities associated with an extra autosome are brought about not only by over-expression of genes present in three doses, but also by modifications in the expression of genes present in the normal two doses. (+info)
Investigation of a unique male and female sibship with Kallmann's syndrome and 46,XX gonadal dysgenesis with short stature.
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A sibship is described where the brother and a sister both have Kallmann's syndrome (anosmia and deficiency of gonadotrophin releasing hormone) and the woman also has streak ovaries. Although there are several conditions that may occur with Kallmann's syndrome, there are no known reports of ovarian dysgenesis being associated with this disorder. Cytogenetic analysis showed no rearrangement or major deletions of the chromosomes. Linkage analysis using informative microsatellite markers predicts that a gene other than KAL1 (at Xp22.3) is implicated in the Kallmann's syndrome manifesting concurrently with ovarian dysgenesis found in this family. (+info)
Maternally inherited cardiomyopathy: clinical and molecular characterization of a large kindred harboring the A4300G point mutation in mitochondrial deoxyribonucleic acid.
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OBJECTIVES: The purpose of this study was to describe the clinical and molecular features of a large family with maternally inherited cardiomyopathy (MICM). BACKGROUND: Recently, several mitochondrial deoxyribonucleic acid (mtDNA) point mutations have been associated with MICM. However, the distinctive clinical and morphologic features of MICM are not fully appreciated. This is partially due to the small size of the reported pedigrees, often lacking detailed clinical and laboratory information. METHODS: Clinical and genetic analysis of the family was carried out. RESULTS: Echocardiography showed mostly symmetrical hypertrophic cardiomyopathy in 10 family members. The illness had an unfavorable course. Progressive heart failure occurred in three subjects, who eventually died; one individual underwent heart transplantation. Electrocardiographic or echocardiographic signs of cardiac hypertrophy in the absence of significant clinical complaints were observed in five subjects. Neurologic examination was normal. The mutation was detected in blood from all available subjects. Abundance of mutated molecules ranged between 13% and 100% of total mtDNA genomes. The severity of the disease could not be foreseen by the proportion of mutation in blood. CONCLUSIONS: This report contributes a better description of the clinical aspects of MICM and provides important clues to distinguish it from hypertrophic cardiomyopathy. We suggest that mtDNA mutations, particularly in the transfer ribonucleic acid for isoleucin, should be systematically searched in patients with MICM. The identification of an underlying maternally inherited mitochondrial DNA defect in familial cases of cardiomyopathy may considerably influence the management and genetic counseling of affected patients. (+info)
Developmental and genetic disorders in spermatogenesis.
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The most common cause of male infertility is idiopathic. Fresh insights based on genetic and molecular analysis of the human genome permit classification of formerly unexplained disorders in spermatogenesis. In this article, we review new procedures that expand diagnostic and therapeutic approaches to male infertility. Recombinant DNA technology makes it possible to detect specific chromosomal and/or genetic defects among infertile patients. The identification of genes linked to disorders in spermatogenesis and male sexual differentiation has increased exponentially in the past decade. Genetic defects leading to male factor infertility can now be explained at the molecular level, even though the germ cell profile of infertile patients is too variable to permit classification of the clinical phenotype. Increasing knowledge of genes that direct spermatogenesis provides important new information about the molecular and cellular events involved in human spermatogenesis. Molecular analysis of chromosomes and/or genes of infertile patients offers unique opportunities to uncover the aetiology of genetic disorders in spermatogenesis. Increasing numbers of cases, previously classified as idiopathic, can now be diagnosed to facilitate the treatment of infertile men. Advanced knowledge also poses ethical dilemmas, since children conceived with assisted reproductive technologies such as intracytoplasmic sperm injection (ICSI) are at risk for congenital abnormalities, unbalanced complements of chromosomes and male infertility. (+info)
Type and frequency of chromosome aberrations in 781 couples undergoing intracytoplasmic sperm injection.
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Cytogenetic investigations were performed in 781 couples prior to intracytoplasmic sperm injection (ICSI) because of severe male infertility or fertilization failures in previous in-vitro fertilization attempts. Out of these 1562 patients, 1012 had a normal karyotype without any aberrations (64.8%), 204 patients had an abnormal karyotypes (13.1%). These chromosome aberrations included constitutional aberrations (4.4%), fragile sites of autosomes (3.0%), low level mosaicism of sex chromosomes (4.0%) and secondary structural chromosome aberrations (4.2%). Combinations of different types of abnormalities were stated. Another 346 patients (22.1%) showed single cell aberrations; the significance of these is unclear at the moment. Constitutional chromosome aberrations were detected in 69 patients. The following chromosome aberrations were observed: 35 sex chromosomal aberrations (comprising hyperploidies of X or Y chromosomes, mosaicisms and derivative X and Y chromosomes), 34 autosomal aberrations including 14 reciprocal translocations, five Robertsonian translocations, six inversions, one marker chromosome, one trisomy 18 mosaicism and seven other structural aberrations. Three autosomal regions showed fragile sites: 6q13 in 2.9% of the patients, 17p12 and 10q24 in 0.05% each. In conclusion, our data show that a high number of infertile couples in an ICSI programme are affected by chromosome aberrations which occur in both sexes. It is suggested that a chromosomal analysis should be performed on both partners before ICSI treatment is initiated. (+info)
Transmission of a Y chromosomal deletion involving the deleted in azoospermia (DAZ) and chromodomain (CDY1) genes from father to son through intracytoplasmic sperm injection: case report.
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The transmission of a deleted in azoospermia (DAZ) deletion from a severely oligozoospermic patient to his son following intracytoplasmic sperm injection (ICSI) treatment is reported. The case report highlights the fertilizing capacity of spermatozoa carrying Y chromosome deletions in patients treated with ICSI and stresses the importance of genetic counselling in severe male infertility. (+info)