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E Schwinger

Publications and source records attributed to E Schwinger.

At least 19 recordsLinked to original sources
PubMed1998

Mutation of the start codon in the FRDA1 gene: linkage analysis of three pedigrees with the ATG to ATT transversion points to a unique common ancestor.

Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder caused by loss-of-function mutations in the gene encoding frataxin. Most patients with FRDA have trinucleotide repeat expansions in both alleles of the FRDA 1 gene. In patients heterozygous for the expansion the second allele may be inactivated by a point mutation. We identified the ATG-->ATT (M11) mutation of the start codon in three independent families. Individuals with symptoms of FRDA in these families are compound heterozygous for the repeat expansion and the ATG mutation. To look for a common founder of the M11 mutation, a detailed linkage analysis employing six polymorphic chromosome 9 markers was performed. We found complete haplotype identity for two of the three chromosomes with the point mutation. The third case shows partial conformity and may be the result of a single recombination event.

Adaptor Proteins, Signal Transducing↗
PubMed1998

HLA-DQB1 and HLA-DPB1 genotypes in familial sarcoidosis.

Numerous reports on the familial occurrence of sarcoidosis, on regionally different prevalences and on its associations with genetic polymorphisms point to the existence of predisposing genes. We have started to establish a collection of DNA from families with two or more sarcoidosis patients for the purpose of genetic linkage and association studies. In this report we present HLA class II genotypes of affected first-degree relatives from 17 families, including eight instances of affected parent and offspring, six sib pairs, and three sib triplets. Genotyping for HLA-DQB1 revealed an over-representation of DQB1*0603 and DQB1*0604 among alleles shared by affected first degree relatives. The same was found for HLA-DPB1*0201 (Glu69 positive). However, none of the sib triplets had any of these alleles in common.

Family↗
PubMed1997

CAG repeat analyses in frozen and formalin-fixed tissues following primer extension preamplification for evaluation of mitotic instability of expanded SCA1 alleles.

Neurodegenerative disorders, including spin-ocerebellar ataxias (SCA), Huntington disease (HD) and dentatorubral-pallidoluysian atrophy (DRPLA), are associated with unstable CAG repeats. To investigate the mitotic stability of the repetitive element in the genes for SCA1, SCA3, HD, and DRPLA we extracted DNA from up to 13 tissue samples from four deceased individuals with progressive neurological disorders and neuropathological signs. Due to the formalin fixation of some tissues the genomic DNA was highly degraded and unsuitable for amplification of fragments longer than 150 bp. After size selection and primer extension preamplification, specific analyses could be performed even for expanded alleles. In all four patients the SCA1 mutation could be demonstrated, in one case with remarkable somatic heterogeneity of the elongated allele, whereas alleles of the normal range were stable in all tissues examined.

Adult↗
PubMed1997

Neural tube defects in chromosomally normal and abnormal human embryos.

Neural tube defects (NTDs) were recognized in eight out of 91 intact embryos from spontaneous abortions and in one case of an induced abortion following prenatal diagnosis of a chromosomal disorder. Five of the nine cases showed chromosomal abnormalities. Trisomy 18 and triploidy were associated with spina bifida in three cases, trisomy 7 with parieto-occipital encephalocele and monosomy X with spina bifida and iniencephaly in one case. A sixth anencephalic embryo in which chromosomal analysis was not performed showed a malformation pattern highly suggestive for trisomy 18. Discussion focuses on the high rate and the type of chromosomal abnormalities among spontaneously aborted NTD embryos, on the contrasting phenotype of 45,X conceptions and on the morphogenesis of the different neural tube defects in early development. In view of future early endovaginal ultrasound diagnosis, the changing morphological pattern is exemplified, and ranges from apparently hyperplastic to degenerative alterations of the exposed neural tissue.

Chorionic Villi Sampling↗
PubMed1997

Molecular cytogenetic diagnostics in sperm.

Among other factors contributing to male infertility, chromosomal anomalies are a frequent finding. Investigating 440 males with reduced sperm counts (< 20 x 10(6)/mL) we found 19 males with chromosome abnormalities (aneuploidies and translocations). This frequency of chromosomal aberrations (4.3%) is much higher than in the normal population. We were able to investigate sperm nuclei from seven out of these 19 men with molecular cytogenetic methods. There were two carriers of Robertsonian translocations, two had a constitutional reciprocal translocation and three were XYY males. In addition, one other man with a long history of infertility and a marker chromosome 15 was included. Using fluorescence in-situ hybridization, it was possible to investigate a great number of sperm nuclei in each case. Each translocation case showed a specific mode of chromosomal segregation; confirming the dependence on chromosomes involved and the individual segregation pattern in each patient. The well known elimination of the supernumerary Y-chromosome in XYY males during meiosis was confirmed in our study. Molecular cytogenetic investigations in sperm provide a more reliable risk estimate with respect to the possible injection of chromosomally unbalanced sperm during intracytoplasmatic sperm injection and can be valuable in genetic counselling.

Adult↗
PubMed1996

Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease.

The difficulties in defining the borders of the schizophrenia spectrum is one major source of variance in linkage studies of schizophrenia. The employment of biological markers may prove advantageous. Due to empirical evidence, eye tracking dysfunction (ETD) has been discussed to be the most promising marker for genetic liability to schizophrenia. With respect to the recent progress in genomic scans, which have pointed to the short arm of chromosome 6, we carried out a scan of the 6p21-23 region with 16 microsatellite markers to test for linkage between chromosomal markers and ETD as well as schizophrenia. We tested 5 models of inheritance of ETD and found maximum two-point lod scores of 3.51 for D6S271 and 3.44 for D6S282. By including these markers in a multipoint analysis, a lod score of 4.02 was obtained. In the case of schizophrenia, 7 models were tested; however, with non-significant results. Our findings, together with another recent linkage report, point to the possibility of a second susceptibility locus for schizophrenia which may be located centromeric to the HLA region. Also, the evidence of ETD being a susceptibility marker for schizophrenia receives further support.

Adult↗
PubMed1996

Evidence for a critical region for penoscrotal inversion, hypospadias, and imperforate anus within chromosomal region 13q32.2q34.

Two unrelated patients with small distal deletions of the long arm of chromosome 13 are described, with shawl scrotum and penoscrotal transposition, penoscrotal hypospadias, a reduced perineum, and anal atresia. The patients have small deletions of 13(q32.2qter) and 13(q32q34), respectively. This report and the literature present evidence for one or possibly more gene(s) within region 13q32.2q34 which regulate the development of the ano-genital structures. The clinical spectrum includes bifid or shawl scrotum, hypospadias, biseptate uterus, malplaced and imperforate anus, and common cloaca.

Anus, Imperforate↗
PubMed1996

Short stature in a mother and daughter with terminal deletion of Xp22.3.

Short stature in females is often caused by hemizygosity for the terminal portion of Xp due to monosomy X or a deletion. We report on a mother and daughter with short stature as sole phenotypic abnormality and deletion of bands Xp22.32-p22.33 demonstrated by classic and molecular cytogenetic analysis. In both individuals, the deleted X chromosome was late replicating. Molecular analysis suggested that the deletion is terminal and the breakpoint was localized between the STS and DXS7470 loci in Xp22.32. Chromosome analysis is often done on females with short stature to exclude Ullrich-Turner syndrome. Small deletions, terminal or interstitial, are easily missed by conventional cytogenetic investigation; thus molecular analyses are useful to detect those cases.

Adult↗
PubMed1996

VACTERL with hydrocephalus and branchial arch defects: prenatal, clinical, and autopsy findings in two brothers.

VACTERL association is defined as a combination of vertebral, anal, cardiac, tracheoesophageal, renal and limb anomalies, in particular radial defects. In recent years hydrocephalus was observed in patients with apparent VACTERL association. This particular condition was recognized as a hereditary entity with poor prognosis. Both autosomal recessive and X-linked forms were described. Here we report prenatal, clinical and autopsy findings in 2 brothers with this syndrome, who had, in addition, branchial arch anomalies. The recurrence in this family suggests X-linked inheritance. Branchial arch defects have so far not been described as part of the VACTERL+H syndrome. This observation further supports that a variety of brain anomalies including hydrocephalus associated with VACTERL anomalies represents separate entities with a considerable recurrence risk. The use of the term VACTERL "association" for these conditions is misleading and is discouraged.

Abnormalities, Multiple↗
PubMed1996

Eye tracking dysfunction in families with multiple cases of schizophrenia.

There is increasing evidence that the genetic predisposition for schizophrenia in families affects more individuals than those fulfilling the criteria for schizophrenia. This finding is supposed to be one of the major problems in molecular genetic schizophrenia research, especially when linkage studies are employed. Eye-tracking dysfunction (ETD), which is conceived as a possible phenotypic marker for genetic liability to schizophrenia, may offer considerable advantages. However, there is only little information from families with multiple occurrence of schizophrenia. It is still unclear whether in these families ETD aggregates with diagnoses from the schizophrenia spectrum. This first report from an ongoing study presents the results of 48 individuals from 6 multiplex families. Smooth-pursuit eye movements were recorded by infrared reflectometry and assessed by quantitative measurement techniques. Along with the high degree of psychiatric morbidity in these families, in 56.3% of the individuals ETD was assessed. Reduced mean pursuit gain was present in 39.6%. The distribution of eye-tracking dysfunction resembles the distribution of schizophrenia-related psychiatry morbidity.

Adult↗
PubMed1996

Analysis of sex and delta F508 in single amniocytes using primer extension preamplification.

Reliable sex determination is an inevitable prerequisite in prenatal and preimplantation diagnosis of X-linked diseases. We report on an amelogenin-based nested polymerase chain reaction sexing method that simultaneously amplifies distinguishable fragments from both sex chromosomes. Primers matching a largely homologous region on both sex chromosomes are used that encompass a 177-bp deletion on the Y chromosome. Thus amplification results in X- and Y-specific fragments of different sizes that are resolved simply by agarose gel electrophoresis. We applied our sexing strategy to 102 single amniocytes previously subjected to primer extension preamplification. 95 showed successful amplification (93.14% sensitivity). The genotyping of all successful amplifications (from 42 male and 53 female amniocytes) was found to be correct (100% specificity). None of the media blanks showed amplification products (no false positives). Additional amplification of the locus of the most common cystic fibrosis mutation resulted in 95.1% success: 89 amniocytes (87.3%) showed no mutated allele and 7 (6.9%) were found to be heterozygous for the delta F508 mutation.

Amelogenin↗
PubMed1996

Results of cytogenetic analysis in men with severe subfertility prior to intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is increasingly becoming the treatment of choice for severe male subfertility. Cytogenetic evaluation of men with andrological subfertility reveals an increased incidence of chromosomal abnormalities when compared with the normal population. We performed chromosomal analysis on the male partners of 32 couples referred for andrological subfertility. In two of these men, constitutional chromosomal translocations were diagnosed prior to ICSI [(45,XY,t(21;22)(p11;q11) and 46,XY,t(22;Y)(p11;q12)]. Since ICSI bypasses many potential barriers of fertilization, successful pregnancy can be achieved despite the presence of severely impaired spermatozoa in a population at high risk for chromosomal aberrations. It is well known that the presence of a chromosomal aberration plays a significant role in partial or complete spermatogenic arrest. ICSI does not seem to increase the risk of fetal chromosomal abnormalities when a spermatozoon from a chromosomally normal male is used. To exclude a higher risk for spontaneous abortion and fetal chromosomal abnormalities, we advocate cytogenetic screening of males with severe male subfertility who opt for ICSI.

Adult↗
PubMed1996

Jumping translocation in a phenotypically normal female.

"Jumping translocation" jt refers to a rare type of chromosome mosaic, in which the same portion of a (donor) chromosome is translocated to different (recipient) chromosome sites. Jt have mainly been observed in lymphocyte cultures of patients with hematologic malignancies. We report a phenotypically normal female carrying a mosaic of two cell lines with the Xq26-qter segment translocated to the short arm of chromosomes 15 or 21 in peripheral blood lymphocytes. In skin fibroblasts, only the X/21 translocation was detected. We speculate that recombination between homologous repetitive sequences on non-homologous human acrocentrics may be the cause of such chromosomal rearrangements.

Abnormalities, Multiple↗
PubMed1996

Five novel mutations in the L1CAM gene in families with X linked hydrocephalus.

Five novel mutations have been identified in the gene encoding L1CAM, a neural cell adhesion protein, in families with X linked hydrocephalus (XHC). Interestingly, all five mutations are in the evolutionarily highly conserved Ig-like domains of the protein. The two frameshift mutations (52insC and 955delG) and the nonsense mutation (Trp276Ter) most probably result in functional null alleles and complete absence of L1CAM at the cell surface. The two missense mutations (Tyr194Cys and Pro240Leu) may considerably alter the structure of the L1CAM protein. These data provide convincing evidence that XHC is genetically extremely heterogeneous.

Abnormalities, Multiple↗
PubMed1996

[Familial occurrence of oculoauricolovertebral dysplasia and Franceschetti syndrome].

Oculoauriculovertebral dysplasia (OAV) and the Franceschetti syndrome (FS) are well-known complexes of anomalies that have dysplasias of the external ear as a common occurrence. In this study the specific patterns of symptoms and familial occurrences of 100 patients with external ear dysplasias were examined (88 patients with OAV dysplasia and 12 patients with FS). Analyzing the pedigree data of the probands, we ascertained the relatives with striking symptoms and associated anomalies of OAV dysplasia. The aim of this study was to determine the influence of genetic transmission on OAV dysplasia in comparison to FS. A striking family history was found in 66.6% of the patients with FS. In 26.1%, family members of patients with OAV dysplasia had external ear dysplasias or other striking symptoms of OAV dysplasia. In this complex of anomalies we also found a higher frequency of skeletal deformities and congenital heart defects than in the normal population. On the basis of our results we suggest that there is a genetic transmission in patients with FS as well as in some cases with OAV dysplasia. Our findings show that it is absolutely necessary to analyze family history very carefully when discussing the recurrence risk or risk of genetic transmission.

Adolescent↗
PubMed1995

[45,X/46,XY/47,XXY chromosome mosaicism as a cause of hypergonadotropic hypogonadism diagnosed in late middle age].

UNLABELLED: HISTORY AND FINDINGS ON EXAMINATION: A 62-year-old man complaining of increasingly painful swelling in both breasts over the previous 6 months was admitted to hospital because an endocrine tumour or paraneoplasia was suspected. Unmarried and childless he had always been well except for mild diabetes treated with glibenclamide. On examination both breasts were enlarged with easily palpable glandular tissue; the testes were small and atrophic. Hair growth and distribution were normal. LABORATORY TESTS: Serum testosterone concentration was low (1.3 ng/ml), while luteinizing and follicle-stimulating hormones (27.3 mU/ml and 95 mU/ml, respectively) were raised. Chromosome analysis revealed 45,X/46,XY/47,XYY mosaicism without evidence of structural aberrations. Mammography showed true gynecomastia without signs of malignancy. TREATMENT AND COURSE: Hypergonadotrophic hypogonadism having been diagnosed the patient was given substitution treatment with 250 mg testosterone, 250 mg i.m. every 3 weeks. The concentrations of luteinizing and follicle-stimulating hormones became normal and the gynecomastia regressed over the subsequent 6 months. CONCLUSION: Mosaicism of the sex chromosomes should be considered in the differential diagnosis of late-onset hypogonadism, even in phenotypically unremarkable men.

Age Factors↗