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Biomedical subjects

P Miny

Publications and source records attributed to P Miny.

At least 19 recordsLinked to original sources
PubMed2002

[Screening for aneuploidy by first trimester nuchal translucency measurement: results from a prospective trial including 1980 cases in a single center in Switzerland].

AIM: The purpose of this study was to evaluate the efficiency of first trimester screening for chromosomal abnormalities using the sonographically determined thickness of nuchal translucency (NT) combined with maternal age. PATIENTS AND METHODS: Risk screening was offered to all patients with a fetal crown rump length (CRL) between 45 and 84 mm after extensive counselling. For the risk assessment the software provided by the Fetal Medicine Foundation was used. In accordance with the recommendation of the Swiss Working Group on First Trimester Screening a cut-off risk of 1 : 400 was chosen. RESULTS: A total of 1980 consecutive pregnancies participating in the risk screening programme with due dates prior to May 1, 2001 were included. Mean maternal age was 30.1 yrs and 522 (26.4 %) patients were 35 yrs or older. A positive risk screening result was obtained in a total of 219 (11.1 %) pregnancies including 33 of the 37 (1.9 %) cases with unbalanced chromosomal abnormalities. CONCLUSIONS: The detection rate for unbalanced chromosome abnormalities in general (89.2 %) as well as the one for trisomy 21 (93.3 %) in particular are very high with a moderate false-positive rate (9.6 %) in this series. As a comparison in the series presented here, traditional "maternal age screening" (cut-off age 35 yrs) would have yielded detection rates of 64.9 % for all unbalanced chromosome abnormalities and 73.3 % for trisomy 21 at a false-positive rate of 25.0 %. Reducing the false-positive rate by raising the cut-off age to 38 yrs would yield detection rates of 40.5 % for all unbalanced chromosome abnormalities and 46.7 % for trisomy 21 at a false-positive rate of 8.9 %. The number of invasive procedures performed to detect one unbalanced chromosome count may be calculated as 21.75 using the cut-off age of 35 yrs as compared to 6.4 using NT measurement and maternal age. The outcome of this ongoing study is in good accordance with the earlier observation that the main benefit of the addition of first trimester NT measurements to the risk screening protocol is a very high detection rate at a moderate false-positive rate.

Adult↗
PubMed2001

Myomectomy during the first trimester associated with fetal limb anomalies and hydrocephalus in a twin pregnancy.

OBJECTIVES: To present the complications of a twin pregnancy after first trimester myomectomy and to discuss the possible etiologic relationship. CASE REPORT: A 44-year-old primigravida with a dichorionic-diamniotic twin pregnancy underwent myomectomy in another hospital at 12 weeks' gestational age. At 28 weeks the patient was referred to our unit because of ventriculomegaly and limb anomalies in the second twin. The patient underwent a Caesarean section at 37 weeks of gestation delivering twin A, a healthy female weighing 3235 g and twin B, a female weighing 2810 g with hydrocephalus and limb anomalies (clubfeet and hypoplasia of the nails and terminal phalanges). The placenta from twin A was normal, but in the placenta of twin B haemorrhage, thrombosis and infarction were noted. CONCLUSIONS: Despite several reports of myomectomy in pregnancy without any problems for mother and fetus, the authors believe that myomectomy - especially in the first trimester - may be associated with the type of problems observed in the present case. The pathophysiological relationship between placental trauma and haemodynamic alterations as a possible cause of the malformations in twin B is discussed.

Adult↗
PubMed2001

Fanconi anemia associated with increased nuchal translucency detected by first-trimester ultrasound.

Increased nuchal translucency between 10 and 14 weeks of gestation has now been established as a marker for chromosomal defects in several large-scale studies. In addition, a growing number of structural defects and some rare genetic syndromes have been identified in association with this marker. We describe a case of a fetus with increased nuchal translucency at 12 weeks of gestation, in which second-trimester evaluation by ultrasound showed an enlarged cisterna magna, a ventricular septal defect and moderate signs of dysmorphia. Karyotyping by chorionic villus sampling revealed a high rate of chromosomal breaks. The diagnosis of Fanconi anemia with early onset was confirmed following the development of severe postnatal anemia 2 months after birth.

Abnormalities, Multiple↗
PubMed2001

A novel syndrome involving primary skeletal growth and retardation in siblings.

An identical pattern of malformations was found in two brothers both having microcephaly and severe developmental delay. Additionally, they had hypotelorism, epicanthic folds, and convergent strabismus. There was shortening of either the radius or the tibia and shortening of the first metacarpals. Persistently dorsally flexed fingers and toes were noted, all of which are unusually long. Both boys had a high-pitched voice and were unable to communicate verbally at the age of 4.5 years. They both developed short stature. One brother has anal atresia; the other had a pulmonary artery atresia, VSD, ASD, and an over-riding aorta. This apparently new syndrome is possibly an autosomal, or a X-linked recessive trait.

Anus, Imperforate↗
PubMed2000

Assessing the chromosome copy number in metaphase II oocytes by sequential fluorescence in situ hybridization.

PURPOSE: Aneuploidy in oocytes is the main cause of failed embryo implantation and of miscarriage. At present, only limited data on the prevalence of aneuploidy in freshly collected human oocytes are available and all studies have been performed with conventional methods for karyotyping. In this feasibility study, multiple-hybridization fluorescence in situ hybridization (FISH) was evaluated as an alternative method to determine the number of chromosomes in oocytes. METHODS: Fifty-two spare oocytes were collected from 23 patients treated with gonadotropins for intrauterine insemination or intracytoplasmic sperm injection. A conventional dual color FISH approach using mixtures of chromosome-specific standard alpha-satellite probes was applied consecutively to the chromosomes of the same metaphase II oocyte. Mixtures of three to six probes were designed in order to allow chromosome identification based on signal color and centromeric index. RESULTS: One hybridization cycle was possible in 52 uninseminated metaphase II oocytes, two hybridizations in 43 oocytes (82.7%), three hybridizations in 30 oocytes (57.6%), four hybridizations in 27 oocytes (51.9%), and five hybridizations in 15 oocytes (28.8%). Altogether, 591 chromosomes could be marked (47.4% of the entire chromosome complement, 11.4 chromosomes per oocyte). The most important single factor contributing to technical failure was loss of the oocyte from the slide. CONCLUSION: This feasibility study demonstrates that multiple-hybridization FISH can be used for the assessment of a larger proportion of the chromosome complement in oocyte as compared to previous studies based on FISH.

Adult↗
PubMed2000

Autosomal recessive disorder otospondylomegaepiphyseal dysplasia is associated with loss-of-function mutations in the COL11A2 gene.

Otospondylomegaepiphyseal dysplasia (OSMED) is an autosomal recessive skeletal dysplasia accompanied by severe hearing loss. The phenotype overlaps that of the autosomal dominant disorders-Stickler and Marshall syndromes-but can be distinguished by disproportionately short limbs, severe hearing loss, and lack of ocular involvement. In one family with OSMED, a homozygous Gly-->Arg substitution has been described in COL11A2, which codes for the alpha2 chain of type XI collagen. We report seven further families with OSMED. All affected individuals had a remarkably similar phenotype: profound sensorineural hearing loss, skeletal dysplasia with limb shortening and large epiphyses, cleft palate, an extremely flat face, hypoplasia of the mandible, a short nose with anteverted nares, and a flat nasal bridge. We screened affected individuals for mutations in COL11A2 and found different mutations in each family. Individuals from four families, including three with consanguineous parents, were homozygous for mutations. Individuals from three other families, in whom parents were nonconsanguineous, were compound heterozygous. Of the 10 identified mutations, 9 are predicted to cause premature termination of translation, and 1 is predicted to cause an in-frame deletion. We conclude that the OSMED phenotype is highly homogenous and results from homozygosity or compound heterozygosity for COL11A2 mutations, most of which are predicted to cause complete absence of alpha2(XI) chains.

Adult↗
PubMed2000

Characterization of an immortalized human granulosa cell line (COV434).

We have investigated the biological characteristics of an immortalized granulosa cell line (COV434), which may be used to study follicular and oocyte maturation in vitro. Granulosa cell function was defined as consisting of three distinct properties: (i) production of 17beta-oestradiol in response to follicle stimulating hormone (FSH); (ii) presence of specific molecular markers of apoptosis enabling the induction of follicular atresia; and (iii) capacity to form intercellular connections with cells surrounding an oocyte. The addition of FSH to the culture medium supplemented with 10% fetal calf serum and 4-androstene-3,17-dione resulted in proliferation of the COV434 granulosa cells and in an increased synthesis of 17beta-oestradiol, indicating the presence of the FSH receptor and cytochrome P450 aromatase in these cells. The receptor for luteinizing hormone (LH) was undetectable. Similar expression of various apoptosis-associated genes was found in COV434 granulosa cells and in granulosa cells of patients stimulated with gonadotrophins for in-vitro fertilization, thus indicating that the immortalized COV434 granulosa cells were able to sustain apoptosis. Multiple intercellular connections were formed during co-culture of COV434 granulosa cells with cumulus cells containing an immature oocyte but not with cumulus cells devoid of an oocyte. Detailed morphological analysis of the intercellular connections with scanning electron microscopy and confocal light microscopy demonstrated the presence of long slender structures. It is concluded that the immortalized human granulosa cell line COV434 may be useful for experimental studies on follicular development.

Apoptosis↗
PubMed2000

Parental origin and mechanisms of formation of cytogenetically recognisable de novo direct and inverted duplications.

Cytogenetic, FISH, and molecular results of 20 cases with de novo tandem duplications of 18 different autosomal chromosome segments are reported. There were 12 cases with direct duplications, three cases with inverted duplications, and five in whom determination of direction was not possible. In seven cases a rearrangement between non-sister chromatids (N-SCR) was found, whereas in the remaining 13 cases sister chromatids (SCR) were involved. Paternal and maternal origin (7:7) was found almost equally in cases with SCR (3:4) and N-SCR (4:3). In the cases with proven inversion, there was maternal and paternal origin in one case each. Twenty three out of 43 cytogenetically determined breakpoints correlated with common or rare fragile sites. In five cases, including all those with proven inverse orientation, all breakpoints corresponded to common or rare fragile sites. In at least two cases, one with an interstitial duplication (dup(19)(q11q13)) and one with a terminal duplication (dup(8) (p10p23)), concomitant deletions (del(8) (p23p23.3) and del(19)(q13q13)) were found.

Abnormalities, Multiple↗
PubMed2000

The long-term effect of external quality assessment on performance in service cytogenetics.

In 1993 a nationwide cytogenetic external quality assessment program (EQA) was initiated in the Federal Republic of Germany. Presently, some 70 laboratories, representing approximately 90% of all cytogenetic diagnostic tests, are participating in the study. Based on the quality assessment scheme of the Association of Clinical Cytogeneticists (1988) in the United Kingdom, quality of chromosome preparation and speed of routine diagnostic services are being evaluated. As a result of continuous external quality assessment, the mean banding level of participating laboratories rose from below 400 bands per haploid set (bphs) in 1994 to approximately 450 bphs in 1999 in prenatal tests and from about 400 to approximately 500 bphs in postnatal tests over the same 5-yr period. The percentage of participants achieving a banding level of 400 bphs or higher rose from approximately 50% to 93% in prenatal tests and from 60% to 96% in postnatal tests. No significant differences were observed in banding scores achieved by private laboratories compared to university institutes. The impact of the assessment of interpretation, reporting, and documentation remains difficult to evaluate. Preliminary data point to a more stringent adherence to ISCN nomenclature in karyotype designation by participants.

Chromosome Aberrations↗
PubMed1999

[Is sterility a genetic burden?].

Genetic causes of infertility are probably not rare. Today only a fraction of genes directly or indirectly involved in reproduction including sex determination and differentiation are known. Nevertheless, the list of well-defined genetic disorders impairing fertility is impressing already today and growing rapidly. Gonosomal aneuploidy and structural rearrangements represent a significant portion of the genetic causes of infertility in both sexes. Other chromosomal conditions include autosomal balanced structural changes (e.g. translocations), probably due to pairing disturbances of the affected chromosomes during meiosis. Some fundamental mechanisms in sex determination and differentiation have been characterized in recent years. Mutations in some of the genes involved in this process may lead to familial infertility. Genetic defects in gametogenesis of both sexes are currently being investigated using mouse models. Male specific causes of infertility include microdeletion within the AZF region of the euchromatic part of the long arm of the Y chromosome and obstructive azoospermia due congenital aplasia of the vas deferens in the presence of mutations in the CFTR gene.

Animals↗
PubMed1999

International, collaborative assessment of 146,000 prenatal karyotypes: expected limitations if only chromosome-specific probes and fluorescent in-situ hybridization are used.

The development of chromosome-specific probes (CSP) and fluorescent in-situ hybridization (FISH) has allowed for very rapid identification of selected numerical abnormalities. We attempt here to determine, in principle, what percentage of abnormalities would be detectable if only CSP-FISH were performed without karyotype for prenatal diagnosis. A total of 146 128 consecutive karyotypes for prenatal diagnosis from eight centres in four countries for 5 years were compared with predicted detection if probes for chromosomes 13, 18, 21, X and Y were used, and assuming 100% detection efficiency. A total of 4163 abnormalities (2.85%) were found including 2889 (69. 4%) (trisomy 21, trisomy 18, trisomy 13, numerical sex chromosome abnormalities, and triploidies) which were considered detectable by FISH. Of these, 1274 were mosaics, translocations, deletions, inversions, rings, and markers which would not be considered detectable. CSP-FISH is a useful adjunct to karyotype for high risk situations, and may be appropriate in low risk screening, but should not be seen as a replacement for karyotype as too many structural chromosome abnormalities will be missed.

Chromosome Aberrations↗
PubMed1998

Low rates of pregnancy termination for prenatally diagnosed Klinefelter syndrome and other sex chromosome polysomies.

Over the past 9 years we counseled 55 couples whose unborn child was found to carry a sex chromosome polysomy. We performed a survey of postcounseling parental decisions about continuation or termination of these pregnancies. Of the 55 embryos or fetuses, 23 had the karyotype 47,XXY, 10 had 47,XYY, and 12 had 47,XXX. In addition, there were 10 instances of true mosaicism, i.e. 47,XXY/46,XY (n = 5), 47,XYY/46,XY (n = 2), or 47,XXX/46,XX (n = 3). Mean gestational age (+/-standard deviation) at diagnosis was 18.3+/-3.0 weeks. After comprehensive genetic counseling 48 (87.3%) of these pregnancies were carried to term. In seven cases (12.7%) the parents elected a pregnancy termination. Two of 31 pregnancies (6.5%) primarily ascertained at our center were aborted, whereas amongst the 24 referred cases, 5 couples (20.8%) opted for a termination. The mean gestational age of the terminated pregnancies was 19.7 weeks. The overall termination rate of 12.7% appears low in comparison with literature data. Most reports from other institutions present termination rates between 32 and 66%. The reason for the low rate of induced abortions in our study cohort is not clear. Cultural differences in parental perception of sex chromosomal polysomies may be of importance, and peculiarities of genetic counseling at our institution could also play a role. Although counseling was nondirective, we did put emphasis on providing prospective parents with information from unbiased follow-up studies of children with Klinefelter syndrome and other sex chromosome polysomies.

Abortion, Induced↗
PubMed1995

Parental origin of the extra haploid chromosome set in triploidies diagnosed prenatally.

The parental origin of the additional chromosome complement in a total of 17 cases of triploidy was determined mainly using highly polymorphic microsatellites. Maternal origin of the triploidy was demonstrated in most cases. To the best of our knowledge, this is the first systematic evaluation of the parental origin of chromosome sets in fetuses who survived until a cytogenetic diagnosis was established. In contrast to previous investigations this study documented a predominance of maternal origin of the extra haploid set mainly due to longer survival time for digynic triploidies. The concept of 2 distinct fetal phenotypes in triploidy is clearly supported by this study.

Adult↗
PubMed1995

Congenital heart disease in the 48,XXYY syndrome.

We report on an infant with severe tetralogy of Fallot, bilateral preauricular pits, and a 48,XXYY chromosomal complement. This case and evidence collected from the literature suggest that congenital heart disease may occur in the 48,XXYY syndrome more frequently than currently appreciated.

Heart Defects, Congenital↗
PubMed1995

[Prenatal diagnosis].

A growing number of methods for the in-utero diagnosis of fetal disease became available during recent decades, mainly due to rapid advances in ultrasound technology and laboratory methods. Exclusion of fetal aneuploidy in pregnancies of women beyond 34 years is still by far the most common reason for an invasive procedure event at a time when the number of diagnosable inborn errors of metabolism and monogenetic disorders is increasing rapidly. Great efforts have been made to improve the poor predictive value of maternal age as an indicator for an increased risk for fetal aneuploidy. Maternal serum screening using various parameters [e.g. AFP, hCG, uE3] has been found effective in identifying the majority of pregnancies with Down syndrome in the second trimester. Current research goals are the optimal choice of markers and the introduction of maternal serum screening in the first trimester of pregnancy. Ultrasound is another suitable tool to identify pregnancies at high risk for aneuploidy at least in the hands of experienced operators. The diagnostic use of fetal cells in the maternal circulation is presently investigated in a large collaborative trial. Second trimester amniocentesis still is the most widely applied invasive technique in pregnancies with maternal age related risks for fetal aneuploidy. Safety and diagnostic accuracy are well established and amniotic fluid can easily be shipped. Without major changes in conventional sampling and laboratory techniques the procedure can be performed at 13 weeks of gestation and later. The safety and efficacy of first-trimester amniocentesis has still to be established in larger series. First-trimester chorionic villus sampling is a well-established alternative to amniocentesis with comparable procedure-related risks. It is the method of first choice in pregnancies at high risk for aneuploidy, inborn errors of metabolism and monogenic disorders, since uncultured villi can be used for a rapid diagnosis. Placental biopsy should also be considered in the second and third trimester of pregnancy for these indications whenever time is a critical issue. Fetal blood obtained by ultrasound-guided cordocentesis has successfully been used for the diagnosis of fetal infection and is at the same time another good source of cells for rapid karyotyping. Other invasive procedures such as fetal skin or liver biopsies for electron microscopy or specific metabolic tests are restricted to the relatively rare instances of diseases where DNA diagnosis is currently not available or uninformative. Providing information on the different alternatives in an individual situation is one of the critical issues in pregnancy care today.

Amniocentesis↗