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Biomedical subjects

D Meschede

Publications and source records attributed to D Meschede.

At least 37 records · Page 2Linked to original sources
PubMed1998

Chromosome abnormalities in 447 couples undergoing intracytoplasmic sperm injection--prevalence, types, sex distribution and reproductive relevance.

Chromosomal abnormalities are thought to be a major contributor to the genetic risks of infertility treatment by intracytoplasmic sperm injection (ICSI). Apart from abnormalities arising de novo, abnormal karyotypes in pregnancies conceived through assisted reproductive technology may be directly derived from predisposing parental aberrations. In a prospective study we have analysed the chromosomes of 868 male and female patients prior to planned ICSI treatment. A total of 33 aberrant karyotypes was diagnosed, corresponding to an abnormality rate of 7.6% per couple or 3.8% per individual studied. Even though male factor infertility was twice as common as female factor infertility in this cohort, 24 of the chromosomal abnormalities were found among the women. Low-level mosaicism for numerical sex chromosome anomalies was diagnosed in 20 individuals, and one patient had the triple X karyotype. With respect to structural chromosomal anomalies, we found six reciprocal and three Robertsonian translocations, two paracentric inversions and one marker chromosome. Many of the aberrations that we diagnosed could be classified as carrying only a small to moderate reproductive risk. Given the high rate of abnormal karyotypes among the female subjects, we suggest that not only the males, but both partners should be routinely karyotyped prior to ICSI.

Adult↗
PubMed1998

Three novel SRY mutations in XY gonadal dysgenesis and the enigma of XY gonadal dysgenesis cases without SRY mutations.

Mutations in the Y-located testis-determining gene SRY are one cause for XY sex reversal. We have previously identified four SRY mutations in a total of 45 sex-reversed females with XY gonadal dysgenesis (XY GD). In a new sample of 16 XY GD cases, three previously undescribed SRY mutations were identified. Two are point mutations that lead to amino acid substitutions in the HMG domain of SRY, M64R, and F67V. The third SRY mutation is a single base insertion 5' to the HMG box within codon 43, converting this lysine codon to a stop codon (K43X). A total of 33 SRY mutations have so far been described that account for only 10-15% of XY GD females. A further 10-15% of these cases result from deletion of SRY due to aberrant X/Y interchange. The etiology of the remaining 70-80% of XY GD cases is still enigmatic. Possible explanations for these XY sex-reversal cases are discussed.

Adolescent↗
PubMed1998

Azoospermia and segmentation abnormalities of the cervicothoracic spine ('MURCS in the male').

The MURCS association is traditionally regarded as a disorder limited to the female sex. It has been hypothesized that men displaying the combination of azoospermia, segmentation abnormalities of the cervicothoracic spine and renal anomalies may have a male analogue of MURCS. Here we describe a patient with non-obstructive azoospermia and Klippel-Feil anomaly type II and suggest that this may represent another case of 'MURCS in the male'.

Abnormalities, Multiple↗
PubMed1998

Strong preference for non-invasive prenatal diagnosis in women pregnant through intracytoplasmic sperm injection (ICSI)

Intracytoplasmic sperm injection (ICSI) is a new and most powerful technique to treat severe forms of human infertility. While the follow-up studies have not shown an increased malformation risk so far, the genetic implications of ICSI are still not fully understood. For this reason, many institutions routinely recommend or even enforce invasive prenatal tests after successful intracytoplasmic sperm injection. We have counselled 107 women pregnant through ICSI about prenatal diagnosis. Sixty-five had already received genetic counselling prior to the treatment (group 1), while 42 had not attended our clinic before (group 2). They were free to choose between invasive and non-invasive diagnosis or no prenatal tests at all. Fifty-four per cent of these patients had an indication for prenatal karyotyping or other invasive procedures independent of ICSI. Only 17 per cent of the total cohort made use of amniocentesis or fetal blood sampling, 82 per cent opted for non-invasive tests (ultrasound, serum screening), and one couple did not wish any prenatal studies. The preference for non-invasive procedures was stronger in group 1 (94 per cent) than in group 2 (65 per cent). We suggest that if patients pregnant through ICSI have the option to choose freely between invasive and non-invasive prenatal tests, they strongly favour the latter.

Adult↗
PubMed1997

Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens.

Congenital absence of the vas deferens (CAVD) is a frequent cause for obstructive azoospermia and accounts for 1%-2% of male infertility. A high incidence of mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has recently been reported in males with CAVD. We have investigated a cohort of 106 German patients with congenital bilateral or unilateral absence of the vas deferens for mutations in the coding region, flanking intron regions and promotor sequences of the CFTR gene. Of the CAVD patients, 75% carried CFTR mutations or disease-associated CFTR variants, such as the "5T" allele, on both chromosomes. The distribution of mutation genotypes clearly differed from that observed in cystic fibrosis. None of the CAVD patients was homozygous for delta F508 and none was compound heterozygous for delta F508 and a nonsense or frameshift mutation. Instead, homozygosity was found for a few mild missense or splicing mutations, and the majority of CAVD mutations were missense substitutions. Twenty-one German CAVD patients were compound heterozygous for delta F508 and R117H, which was the most frequent CAVD genotype in our study group. Haplotype analysis indicated a common origin for R117H in our population, whereas another frequent CAVD mutation, viz. the "5T allele" was a recurrent mutation on different intragenic haplotypes and multiple ethnic backgrounds. We identified a total of 46 different mutations and variants, of which 15 mutations have not previously been reported. Thirteen novel missense mutations and one unique amino-acid insertion may be confined to the CAVD phenotype. A few splice or missense variants, such as F508C or 1716 G-->A, are proposed here as possible candidate CAVD mutations with an apparently reduced penetrance. Clinical examination of patients with CFTR mutations on both chromosomes revealed elevated sweat chloride concentrations and discrete symptoms of respiratory disease in a subset of patients. Thus, our collaborative study shows that CAVD without renal malformation is a primary genital form of cystic fibrosis in the vast majority of German patients and links the particular expression of clinical symptoms in CAVD with a distinct subset of CFTR mutation genotypes.

Adult↗
PubMed1997

Screening for deletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in azoospermia and severe oligozoospermia.

OBJECTIVE: To evaluate the occurrence and prevalence of microdeletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in patients with azoospermia or severe oligozoospermia. DESIGN: Controlled clinical study. SETTING: University infertility clinic. PATIENT(S): Infertile men (n = 168) with nonobstructive, idiopathic azoospermia or severe oligozoospermia and normal LH. The control group consisted of proven fathers (n = 86). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis; polymerase chain reaction amplification of the loci sY84, sY143, sY254, and sY255; serum FSH, LH, and T; testicular volume. RESULT(S): Deletions involving the sY254 and sY255 DAZ loci were found in three azoospermic patients and two men with sperm concentration < 1 x 10(6)/mL. Serum FSH was elevated in four patients and was normal in one. All five patients had decreased testicular volumes compared with controls. No deletions involving the sY84 and sY143 loci were found. The four loci were amplified normally in the control group. CONCLUSION(S): The estimated frequency of deletions involving the DAZ locus is 3% in azoospermic-severely oligozoospermic men consulting an infertility clinic. Polymerase chain reaction amplification of the DAZ locus is useful for the diagnosis of microdeletions of the Y chromosome. Deletions involving more proximal regions of the Y chromosome seem to be rare.

Adult↗
PubMed1997

Sex chromosomal anomalies in pregnancies conceived through intracytoplasmic sperm injection: a case for genetic counselling.

The prevalence of sex chromosomal anomalies (SCA) is higher after treatment with intracytoplasmic sperm injection (ICSI) than in naturally conceived pregnancies. This finding is not only important in the debate about the genetic safety of ICSI, it also has repercussions on the design of appropriate strategies for prenatal and preimplantation diagnosis in ICSI pregnancies. We discuss here in detail the developmental prognosis of individuals carrying a sex chromosomal anomaly. Major malformations do occur in Turner syndrome, but not so in Klinefelter, the triple X and the XYY syndromes. Infertility represents an almost obligate finding in Klinefelter syndrome, but the latest developments in microassisted reproduction may help to overcome this problem. Importantly, mental retardation does not occur more often in individuals with an SCA than in normal controls. Academic achievement, however, may be somewhat reduced compared with peers. Overall, for most children carrying a sex chromosomal anomaly, a major congenital handicap is not to be expected, and the long-term developmental prognosis is fairly good. Therefore, if an SCA is diagnosed prenatally in an ICSI pregnancy, an unbiased and detailed discussion of the developmental perspectives is warranted. The option of continuing such a pregnancy should be given due consideration.

Cytoplasm↗
PubMed1997

Intracytoplasmic sperm injection pregnancy with fetal trisomy 9p resulting from a balanced paternal translocation.

Infertile men who carry a chromosomal translocation can be successfully treated with intracytoplasmic sperm injection (ICSI). However, such treatment carries a risk that a pregnancy with an abnormal karyotype will be induced. While in all previously published cases the outcome was favourable, we here report the first instance of a parental reciprocal translocation leading to a chromosomally unbalanced ICSI pregnancy. The fetus, one of a pair of dizygotic twins, was found to have trisomy for the short arm of chromosome 9. The parents opted for selective abortion of the affected twin.

Amniocentesis↗
PubMed1997

The molecular genetics of male infertility.

The important role of genetic abnormalities in the causation of human male infertility is increasingly recognized. While much remains to be learned in this fast moving field, considerable progress has been achieved over the past years both in the clinical delineation of genetic forms of male infertility and in the characterization of the responsible genes and their mutations. We review the current state of knowledge on monogenic disorders where male infertility is a major and regular feature. Clinical and molecular details are given on a total of seventeen such entities. We restrict our survey to disorders that may actually come to the clinical attention of the reproductive medicine specialist.

Abnormalities, Multiple↗
PubMed1997

Genetic counselling for infertile male patients.

A substantial part of the male infertility caseload has a genetic basis. To identify a genetic abnormality in an infertile man is not only important for the patient himself and his offspring, but also for an optimized clinical case management. Laboratory studies (karyotyping, DNA analysis) are often required, but the single most effective diagnostic technique in clinical genetics is taking a meticulous family history. In selected cases a dysmorphological physical examination may be required to recognize a syndromal disorder. The genetic examination may sometimes establish a previously unrecognized diagnosis, and this informs the andrologist about possible risks of an active infertility treatment. However, genetic testing combined with counselling is, above all, intended to be of benefit to the counsellee himself. He should i) be provided with all factual genetic information relevant to his medical situation, and ii) be enabled to reach an informed decision about reproductive goals and strategies, genetic risk taking, and prenatal diagnosis if applicable.

Cytodiagnosis↗
PubMed1996

Isochromosome Xq in Klinefelter syndrome: report of 7 new cases.

In this collaborative study we report on 2 prenatally and 5 postnatally diagnosed cases with a 47,X,i(Xq),Y chromosomal constitution. Excepting tall stature, the 5 adult patients showed all typical manifestations of Klinefelter syndrome. Taken together with previously reported cases, these data suggest that Klinefelter syndrome with isochromosome Xq has a favorable prognosis with normal mental development, and with normal-to-short stature. The prevalence of this Klinefelter variant is calculated to be between 0.3-0.9% in males with X chromosome polysomies.

Adult↗
PubMed1996

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11.

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.

Chromosome Mapping↗