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F Fellmann

Publications and source records attributed to F Fellmann.

14 recordsLinked to original sources
PubMed2005

Segregation of chromosomes in sperm of Robertsonian translocation carriers.

Robertsonian translocations are the most frequent structural chromosomal abnormalities in humans and can affect fertility, with various degrees of sperm alterations in men; or the pregnancy outcome of the carriers. The studies on meiotic segregation of chromosomes in sperm of Robertsonian translocation males find a majority of normal or balanced spermatozoa for the chromosomes related to the translocation (mean 85.42%; range 60-96.60%). Furthermore, recent studies suggest an interchromosomal effect. Studies on spermatozoa from translocation carriers, and in mouse models help the comprehension of the meiotic segregation mechanisms. Results of meiotic segregation analysis in man could be integrated in genetic counselling especially when assisted reproductive technology is required.

Chromosomes, Human, Pair 13↗
PubMed2002

Absence of anti-Müllerian hormone (AMH) and M2A immunoreactivities in Sertoli cell-only syndrome and maturation arrest with and without AZF microdeletions.

BACKGROUND: Some genes identified in the AZF locus are expressed only in germinal cells; others are ubiquitous. AZF microdeletions seem to occur at the earliest stages of ontogenetic development, and one might therefore assume that Sertoli cells preserve some immature characteristics and that their immunophenotype may be modified by the existence of a molecular defect. MATERIALS AND METHODS: Two immunohistological markers of Sertoli cell immaturity [anti-Müllerian hormone (AMH) and M2A] were tested in two histopathological groups (maturation arrest at spermatocyte I stage and Sertoli cell-only syndrome). We analysed 68 testicular samples obtained from 39 patients with non-obstructive azoospermia associated or not with AZF microdeletions. RESULTS: The absence of M2A and AMH immunoreactivity in adult gonads was observed without any correlation to spermatogenetic impairment or molecular deficit in the AZF region. In the samples of these two series, Sertoli cells showed a mature phenotype for AMH and M2A markers. CONCLUSIONS: In patients with AZF microdeletions, the genotype-phenotype correlations seem to be more complex than has been suggested previously; more detailed characterization of the immunohistochemical phenotype associated with the molecular defect may be useful in understanding the spermatogenic failure mechanism.

Adult↗
PubMed2001

Adult hypophosphatasia. Current aspects.

Hypophosphatasia is an inborn metabolic disorder in which abnormally low levels of the enzyme nonspecific alkaline phosphatase result in defective skeletal and dental mineralization (rickets, fractures, dental abnormalities) and in accumulation of the enzyme substrates (phosphoethanolamine, pyridoxal-5'phosphate and inorganic pyrophosphate). The build-up of inorganic pyrophosphate promotes the development of articular chondrocalcinosis. There are several forms of hypophosphatasia, with wide variations in severity. We report the case of a 53-year-old man with typical manifestations of moderate adulthood hypophosphatasia. Investigations in his family found the disease in a sister and two children. He had two autosomal mutations, which were transmitted recessively. Several mutations of the alkaline phosphatase gene have been identified. The genotype is correlated with the phenotype: some mutations are associated with milder forms and others with more severe forms of the disease.

Age of Onset↗
PubMed2001

Meiotic segregation analysis by FISH investigation of spermatozoa of a 46,Y,der(X),t(X;Y)(qter-->p22::q11-->qter) carrier.

Chromosome analysis performed on a 30-year-old man revealed a 46,Y,der(X),t(X;Y)(qter-->p22::q11-->qter) karyotype, confirmed by fluorescence in situ hybridization (FISH). The man was of short stature, and no mental retardation was noticed; genitalia and testes were normal, as were the patient's FSH, LH, and testosterone blood levels. Sperm analysis showed azoospermia at the time of the first sampling and severe oligozoospermia, with 125,000 spermatozoa/milliliter, at the time of the second sampling. The sperm gonosomal complement of this patient and of a 46,XY donor were analyzed using multicolor FISH with X- and Y-chromosome probes. Our results clearly indicated that germinal cells carrying the translocation are able to complete the meiotic process by producing spermatozoa compatible with normal embryonic development, with more than 80% of the spermatozoa having either a Y chromosome or a der(X); however, a high level of spermatozoa with gonosomal disomies was observed. We also found a significant increase in the frequency of autosomal disomies in the carrier, which would suggest an interchromosomal effect. All previously reported cases in adult males were associated with azoospermia; testicular histological studies, performed in patients carrying the same X;Y translocation, showed spermatogenetic arrest after pachytene. To our knowledge, this is the first molecular analysis of the gonosomal complement in spermatozoa of men with a t(X;Y)(qter-->p22::q11-->qter).

Adult↗
PubMed2001

[Repetitive acute pancreatitis in a late-diagnosed cystic fibrosis: prevention of relapses by octreotide in the long term].

We report on the case of a 35 year-old woman who was initially admitted for acute pancreatitis in october 1995. The patient was suffering from asthma (since childhood) and diffuse abdominal pain (since adolescence). The diagnosis of cystic fibrosis was made fortuitously during a sterility evaluation. After extensive etiological screening the acute pancreatitis was considered to be a manifestation of the cystic fibrosis. Despite therapy with pancreatic enzymes, the patient continued to suffer from chronic abdominal pain. High intake of analgesics was required. Until December 1995, the patient was repeatedly admitted for episodes of acute pancreatitis. In January 1996, we initiated a preventive treatment with subcutaneous octreotide between 100 and 200 microgram, three time a day. Thereafter, there were fewer episodes of pancreatitis and the consumption of analgesics decreased. Side effects of octreotide were intermittent diarrhea and development of cholelithiasis that was complicated by biliary migration in November 1998. In June 1999, the prolonged-release form of the molecule was given without modification of the efficacy.

Acute Disease↗
PubMed2000

Fifteen new mutations (-195C>T, L-12X, 298-2A>G, T117N, A159T, R229S, 997+2T>A, E274X, A331T, H364R, D389G, 1256delC, R433H, N461I, C472S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with hypophosphatasia.

Hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and deficiency of serum and liver/bone/kidney-type alkaline phosphatase (L/B/K ALP) activity. We report the characterization of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 12 families affected by severe or mild hypophosphatasia. Twenty distinct mutations were found, 5 of which were previously reported. Nine of the 15 new mutations were missense mutations (T117N, A159T, R229S, A331T, H364R, D389G, R433H, N461I, and C472S). The others were 2 nonsense mutations (L-12X and E274X), one single nucleotide deletion (1256delC), 2 mutations affecting splicing (298-2A>G, 997+2T>A), and a mutation in the major transcription start site (-195C>T). Hum Mutat 15:293, 2000.

Alkaline Phosphatase↗
PubMed2000

AZFa deletions in Sertoli cell-only syndrome: a retrospective study.

Lack of data on the genotype-phenotype relationship in cases of AZF microdeletions is due to the limited number of histological investigations in human male infertility cases. We investigated the possibility of retrospective detection of Yq11 microdeletions by using DNA extracted from diagnostic testicular biopsies. We used histological criteria to select two series of material: 22 biopsies with Sertoli cell-only syndrome and 14 biopsies with maturation arrest at the spermatocyte I stage. Two markers, DFFRY and DAZ, were tested by nested polymerase chain reaction (PCR) in the two series. In the Sertoli cell-only syndrome series, we found four deletions affecting the DFFRY gene (18.2%). In the second series, no deletions were detected. Two conclusions may be considered, although the number of specimens analysed is limited: (i) the frequency of deletions observed in Sertoli cell-only syndrome allows us to suggest that deletion in the AZFa region may be involved in this pathology; and (ii) retrospective studies may yield some additional elements in our search for eventual genotype-phenotype relationships.

Chromosome Deletion↗
PubMed1997

Fortuitous detection of uniparental isodisomy of chromosome 6.

Uniparental isodisomy is defined as the inheritance of two copies of the same parental chromosome and can result in defects when it produces homozygosity for a recessive mutation or in the presence of imprinting. We describe the detection of a chromosome 6 uniparental isodisomy in a 9 year old girl, discovered during a search for an HLA identical sib. HLA typing, erythrocyte phenotyping, and genotypes of microsatellite polymorphisms were compatible with a paternal isodisomy of chromosome 6, with normal biparental origin of the other chromosomes. Paternal cells were not responsive to the patient's cells in mixed lymphocyte cultures. This fortuitous detection of a chromosome 6 isodisomy suggests that cases of chromosome 6 UPD may not be deleterious and may therefore go undetected.

Cells, Cultured↗
PubMed1996

Molecular analysis by fluorescence in situ hybridization of a prenatally detected de novo complex chromosomal rearrangement t(2q;3p;4q;13q).

We report one case of de novo complex chromosomal rearrangement (CCR) t(2q;3p;4q;13q) with at least five chromosomal breakpoints. This CCR was detected prenatally at 22 weeks of gestation, when mild echographic indications were disclosed during a routine examination in a female with no family history of congenital abnormalities. This observation clearly illustrates what the fluorescence in situ hybridization (FISH) technique can offer to the analysis of such rearrangements, together with standard cytogenetic techniques. No chromosomal imbalance was cytologically proved. Nevertheless, the status of the infant at birth and the disorders that he exhibited during the following months demonstrate once again that even in the absence of alarming ultrasonographic verifications and even if standard and molecular cytogenetics do not allow us to confirm evident chromosomal imbalances, genetic counselling in the case of prenatally detected de novo CCR must remain cautious.

Abnormalities, Multiple↗
PubMed1996

Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz and the lethal acrodysgenital syndromes.

UNLABELLED: The Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder characterized by dysmorphic facial features with abnormal limbs and genitalia. Two forms have been recognized based on clinical course and severity: the classical SLO (type I) and the lethal acrodysgenital syndrome (type II). Type I SLO has been recently ascribed to a defect in cholesterol synthesis. Taking advantage of a series of seven patients including five type I and two type II SLO, we describe micrognathia, severe microcephaly, major ante and post natal growth retardation and feeding difficulties as consistent features in the disease. In addition, we give support to the presence of abnormal cholesterol levels in the lethal acrodysgenital syndrome but find no correlation between plasma sterol levels and the clinical severity of the disease. CONCLUSION: The identification of the same biochemical defect in both types of Smith-Lemli-Opitz Syndrome suggests that despite major discrepancies in clinical course and severity, type I and type II SLo are probably allelic disorders.

Child↗
PubMedDate not supplied

French multi-centric study of 2000 amniotic fluid interphase FISH analyses from high-risk pregnancies and review of the literature.

This prospective and multi-centric study confirms the accuracy and the limitations of interphase FISH and shows that any cytogenetics laboratory can perform this technique. With regard to the technical approach, we think that slides must be examined by two investigators, because the scoring may be subjective. The main problem with the AneuVysion kit concerns the alpha satellite probes, and especially the chromosome 18 probe, which is sometimes very difficult to interpret because of the high variability of the size of the spots, and this may lead to false negative and uninformative cases. The best solution would be to replace these probes by locus-specific probes. Concerning clinical management, we offer interphase FISH only in very high-risk pregnancies or/and at late gestational age because of the cost of the test. We think that an aberrant FISH result can be used for a clinical decision when it is associated with a corresponding abnormal ultrasound scan. In other cases, most of the time, we prefer to wait for the standard karyotype.

Adult↗