Editor—Anderson-Fabry disease (AFD) is a sphingolipid storage disorder resulting from the deficiency of the lysosomal enzyme α-galactosidase. Unlike most other lysosomal diseases, the inheritance is X linked. Disease manifestations in female heterozygotes have been reported, but are considered to be rare and usually mild.1 Asymptomatic corneal dystrophy (cornea verticillata and posterior lenticular cataract) is present in about 70% and is useful for heterozygote detection. About 30% of women have minimal angiokeratomas and <10% have infrequent attacks of neuropathic pains.1 However, female heterozygotes with severe and early cerebrovascular disease, strokes, and renal failure have been documented, but these serious manifestations were estimated to occur in only 1%.1 Because this is an X linked disorder, these severe manifestations in females were explained by skewed X inactivation.2 

Case reports are open to selection bias and there are no reported data on the frequency and severity of AFD manifestations in a large cohort of carriers. Women are not usually evaluated in the clinic unless they present with serious AFD complications, but they do attend for genetic counselling when their son or male relative is diagnosed with the disease.

During regular reviews of AFD families in the genetic clinic, we have observed multiple and more frequent AFD manifestations in female carriers than expected. Owing to the lack of clinical data and present health care policy, we were unable to perform clinical investigations. Therefore, a large cohort study using an AFD specific questionnaire was performed to establish the mortality and the frequency of all AFD manifestations in obligate carrier females.

All known (n=80) obligate carrier females, who were over the age of 18 and had demographic data recorded in the AFD register, were asked to participate in this study. Sixty (75%) agreed and provided data; non-responders were reminded on one …

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

Establishment of male-specific epigenetic information.

Infertility – the inability to achieve conception or sustain a pregnancy through to live birth – is very common and affects about 15% of couples. While chromosomal or genetic abnormalities associated

Somatic chromosomal abnormalities in infertile men and women

Pregnancies achieved by assisted reproduction technologies, particularly by intracytoplasmic sperm injection (ICSI) procedures, are susceptible to genetic risks inherent to the male population treated with ICSI and additional risks inherent to this innovative procedure. The documented, as well as the theoretical, risks are discussed in the present review study. These risks mainly represent that consequences of the genetic abnormalities underlying male subfertility (or infertility) and might become stimulators for the development of novel approaches and applications in the treatment of infertility. In addition, risks with a polygenic background appearing at birth as congenital anomalies and other theoretical or stochastic risks are discussed. Recent data suggest that assisted reproductive technology might also affect epigenetic characteristics of the male gamete, the female gamete, or might have an impact on early embryogenesis. It might be also associated with an increased risk for genomic imprinting abnormalities.

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Genetic and epigenetic risks of intracytoplasmic sperm injection method.

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.

Developmental and genetic disorders in spermatogenesis

An apparently balanced reciprocal translocation 46,X,t(Y;6) (q11.23 ∼ q12;p11.1) was observed in an infertile man with severe oligozooteratozoospermia. Different mitotic chromosome banding patterns were performed and fluorescence in situ hybridization indicated a breakpoint in the fluorescent Yq heterochromatin. Molecular genetic deletion experiments for the azoospermia factor region in distal Yq11 showed the retention of the DAZ gene and meiotic pairing configurations suggested that the man’s infertility could be due to the pairing behaviour of the Y;6 translocation chromosome with the X chromosome visualised by synaptonemal complex analysis at the electron microscopy level. The morphological appearance of the normal chromosome 6 and the Y;6 translocated chromosome included in the compartment of the sex vesicle may allow an explanation of the degeneration of most spermatocytes after the pachytene stage.

Ratib Djlelati

Papers

Y-autosome translocation and infertility: usefulness of molecular, cytogenetic and meiotic studies.