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Biomedical subjects

J Murken

Publications and source records attributed to J Murken.

35 records · Page 2Linked to original sources
PubMed1993

Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure.

The X-lined gene for Norrie disease, which is characterized by blindness, deafness and mental retardation has been cloned recently. This gene has been thought to code for a putative extracellular factor; its predicted amino acid sequence is homologous to the C-terminal domain of diverse extracellular proteins. Sequence pattern searches and three-dimensional modelling now suggest that the Norrie disease protein (NDP) has a tertiary structure similar to that of transforming growth factor beta (TGF beta). Our model identifies NDP as a member of an emerging family of growth factors containing a cystine knot motif, with direct implications for the physiological role of NDP. The model also sheds light on sequence related domains such as the C-terminal domain of mucins and of von Willebrand factor.

Amino Acid Sequence↗
PubMed1992

De novo interstitial deletion 16(q12.1q13) of paternal origin in a 10-year-old boy.

A 10-year-old boy with a de novo del(16)(q12.1q13) and many features of the deletion 16q phenotype is described. The deletion occurred in a paternal chromosome as demonstrated by DNA studies with polymorphic (AC)n microsatellite repeat markers. Comparison with published cases suggests that deletion of either of two regions (q13 and q22.1) on the long arm of chromosome 16 is associated with an apparently identical phenotype. No parental imprinting of this region was demonstrated.

Abnormalities, Multiple↗
PubMed1991

Trisomy 18 in chorionic villus sampling: problems and consequences.

Among 1547 patients undergoing first-trimester prenatal diagnosis, 100 fetal chromosome aberrations were detected. Thirteen of these involved chromosome 18. In two structural abnormalities of chromosome 18, the aberration could be excluded in amniotic fluid cells and two healthy infants were born. Trisomy 18 was not confirmed in amniotic fluid cells in three trisomy 18 mosaics. In eight non-mosaic trisomy 18 first-trimester diagnoses, the diagnosis was excluded by amniotic fluid cells or fetal cultures in four, and confirmed in the remaining four. Diagnosis of chromosome 18 aberrations in the direct preparation should be confirmed in the long-term culture of the chorionic villus sample or by amniotic fluid cultures.

Amniocentesis↗
PubMed1991

[Neurogenetics--the challenge for neurology. 1. Neurogenetic diseases].

Progress in molecular genetics has provided insight into a number of neurogenetic disorders. The chromosomal location of the genes for Huntington's disease, Wilson's disease, myotonic dystrophy and Friedreich's ataxia are now known. In families affected by these illnesses, linkage analysis can now be employed for presymptomatic or prenatal diagnosis. The genes for Duchenne and Becker muscular dystrophy and neurofibromatosis I have been cloned and sequenced, allowing the direct analysis of the genetic defect in many cases, and thereby providing further insight into the pathophysiology. In addition, the classification of several neurogenetic diseases, such as the hereditary motor and sensory neuropathies or the spinal muscular atrophies can now be based on the chromosomal location of the affected gene(s).

Chromosome Mapping↗
PubMed1990

Chromosomal in situ suppression hybridization of human gonosomes and autosomes and its use in clinical cytogenetics.

DNA libraries from sorted human gonosomes were used selectively to stain the X and Y chromosomes in normal and aberrant cultured human cells by chromosomal in situ suppression (CISS-) hybridization. The entire X chromosome was stained in metaphase spreads. Interphase chromosome domains of both the active and inactive X were clearly delineated. CISS-hybridization of the Y chromosome resulted in the specific decoration of the euchromatic part (Ypter-q11), whereas the heterochromatic part (Yq12) remained unlabeled. The stained part of the Y chromosome formed a compact domain in interphase nuclei. This approach was applied to amniotic fluid cells containing a ring chromosome of unknown origin (47,XY: +r). The ring chromosome was not stained by library probes from the gonosomes, thereby suggesting its autosomal origin. The sensitivity of CISS-hybridization was demonstrated by the detection of small translocations and fragments in human lymphocyte metaphase spreads after irradiation with 60Co-gamma-rays. Lymphocyte cultures from two XX-males were investigated by CISS-hybridization with Y-library probes. In both cases, metaphase spreads demonstrated a translocation of Yp-material to the short arm of an X chromosome. The translocated Y-material could also be demonstrated directly in interphase nuclei. CISS-hybridization of autosomes 7 and 13 was used for prenatal diagnosis in a case with a known balanced translocation t(7:13) in the father. The same translocation was observed in amniotic fluid cells from the fetus. Specific staining of the chromosomes involved in such translocations will be particularly important, in the future, in cases that cannot be solved reliably by conventional chromosome banding alone.

Chromosome Aberrations↗
PubMed1990

Definitive localization of X-linked Kallman syndrome (hypogonadotropic hypogonadism and anosmia) to Xp22.3: close linkage to the hypervariable repeat sequence CRI-S232.

Kallmann syndrome is a genetically heterogeneous disease characterized by hypogonadotropic hypogonadism and anosmia. Six families in which the disorder followed an X-linked inheritance were investigated by linkage analysis. Diagnostic criteria were uniformly applied and included tests for hypogonadotropic hypogonadism and anosmia. Close linkage was found by using the hypervariable repeated sequence CRI-S232 (DXS278) previously mapped to Xp22.3. At a maximum lod score of 6.5, the recombination fraction was calculated as .03. Of 30 fully informative meioses, one recombination between the disease locus and the loci recognized by probe CRI-S232 was observed. When an independent approach is used, these results confirm the X-linked Kallmann syndrome assignment previously made by deletion mapping, and allow definitive localization of the syndrome assignment previously made by deletion mapping, and allow definitive localization of the syndrome to the Xp22.3 region. This opens the way to carrier detection and to the identification of a gene responsible for this disorder.

Chromosome Mapping↗
PubMed1989

Linkage of X-linked retinitis pigmentosa to the hypervariable DNA marker M27 beta (DXS255).

A hypervariable DNA marker is closely linked to one of the most severe forms of night blindness, X-linked retinitis pigmentosa (RP). Affected individuals with X-linked RP, obligate carriers, and ophthalmologically identifiable carriers of the disease were included in a linkage study. The diagnosis was established in five sibships by funduscopic and electrophysiological investigations. When the X-linked probe M27 beta was used, 2 recombinants out of 29 informative meioses were detected (theta = 0.07 at a maximum lod of 4.75). The hypervariable probe detected two different alleles in 38 of 39 females tested. M27 beta is therefore a potentially very useful probe for carrier detection and prenatal diagnosis, as well as for addressing the question of heterogeneity of X-linked RP.

Female↗
PubMed1989

[Subjective experience of prenatal diagnosis and genetic counseling].

Two surveys (one involving 650, the other 638 women) based upon interviews about the utilization of prenatal diagnosis by clients are reported. First it is demonstrated which factors obstruct a decision for prenatal diagnosis. Then, a contrast is made between the risk attitude of two groups, namely women who underwent amniocentesis or chorion villi biopsy and those respondents who decided against prenatal diagnosis. Finally, how the examination technique (amniocentesis or chorion villi biopsy) influences the experience of pregnancy is discussed.

Adaptation, Psychological↗
PubMed1989

[Psychosocial aspects of the decision to utilize prenatal diagnosis--results of an empirical study].

After undergoing amniocentesis and delivering their child 504 women were asked by questionnaire for their attitude towards and their experience of pregnancy and amniocentesis. The majority of the women reported that they experienced their decision to utilise amniocentesis as largely unproblematic. In most cases they had already come to a decision before genetic counselling resulting from talking things over with their partner and their gynaecologist. The decision was mostly based on risk assessment and less by considerations of potential consequences of the operation. On the other hand, nearly one-quarter of the respondents found it difficult to decide on their line of action. Their decision was taken more often during or after genetic counselling, and their partner disagreed more frequently with amniocentesis. In this group of women there were more respondents who refused an induced abortion if their child was severely handicapped, than in the group without difficulties with their decision. Disadvantages, consequences of the operation, and conflicts stemming from the social environment of the expectant woman were mentioned as additional reasons for difficulties in arriving at a decision. Potential implications for genetic counselling practice are discussed.

Adult↗
PubMed1988

[Change in the course of blindness in childhood].

In the course of the 20th century there have been major changes in the causes of blindness in childhood. This is illustrated by the example of the 1271 children born between 1885 and 1976 who attended the Bavarian State School for the Blind. The following developments became apparent: Until 1940 the most common cause of blindness, accounting for 25% of the cases, was corneal disease, almost exclusively of infectious origin. This cause has been reduced most, to 2%. There has also been a clear reduction in blindness due to anterior uveitis (mainly due to infection) and chorioretinitis. There were fewer such cases -5% and 3%, respectively. Since the 1960s there have been no further cases of blindness due to ocular injury in children, and no case of sympathetic ophthalmia has occurred since 1950. While the incidence of congenital cataract and buphthalmos has remained constant, they now only lead to blindness in a small proportion of those affected, thanks to improvements in therapy. The incidence of blindness caused by retinal detachment, usually associated with myopia, is also unchanged, though rare (2-3%). The same applies to bilateral retinoblastoma, while the frequency of optic nerve atrophy (20%) and tapetoretinal degeneration (16-19%) has remained both constant and high. There has been a drastic increase in ocular malformations and developmental anomalies. These include retrolental fibroplasia, which was responsible for blindness in 38% of the children born between 1967 and 1976. Overall, there has been a major reduction in the number of blind children in the population since the 1960s and especially since the 1970s.

Blindness↗
PubMed1980

[Prenatal diagnosis in parents with a balanced structural chromosome aberration (author's transl)].

By means of 10 case reports, the significance of prenatal diagnosis and the risk for the progeny of parents with a balanced structural chromosomal aberration are demonstrated. The aberrations were ascertained through: a previous malformed child, previous miscarriages or stillbirths or through fetal cell analysis during prenatal diagnosis performed for independent reasons. Theoretical considerations concerning the estimates of risk figures in these families are presented and the currently available risk values which are the basis of the indication for prenatal diagnosis, given.

Adult↗
PubMedDate not supplied

Deletion mapping on chromosome 10p and definition of a critical region for the second DiGeorge syndrome locus (DGS2).

DiGeorge syndrome (DGS) is a developmental field defect, characterised by absent/hypoplastic thymus and parathyroid, and conotruncal heart defects, with haploinsufficiency loci at 22q (DGS1) and 10p (DGS2). We performed fluorescence in situ hybridisations (FISH) and polymerase chain reaction (PCR) analyses in 12 patients with 10p deletions, nine of them with features of DGS, and in a familial translocation 10p;14q associated with midline defects. The critical DGS2 region is defined by two DGS patients, and maps within a 1 cM interval including D10S547 and D10S585. The other seven DGS patients are hemizygous for both loci. The breakpoint of the reciprocal translocation 10p;14q maps at a distance of at least 12 cM distal to the critical DGS2 region. Interstitial and terminal deletions described are in the range of 10-50 cM and enable the tentative mapping of loci for ptosis and hearing loss, features which are not part of the DGS clinical spectrum.

Cell Line, Transformed↗
PubMedDate not supplied

UHX1 and PCTK1: precise characterisation and localisation within a gene-rich region in Xp11.23 and evaluation as candidate genes for retinal diseases mapped to Xp21.1-p11.2.

The gene for ubiquitin hydrolase on the X chromosome (UHX1), cloned and mapped to Xp21.2-p11.2, is a candidate gene for retinal diseases. We used fine mapping techniques to localise UHX1 between markers DXS1266 and DXS337, where congenital stationary night blindness (XICSNB) and retinitis pigmentosa type 2 (RP2) are also located. Reevaluation of the UHX1 gene structure demonstrated five new exons, for a total of 21 exons and a predicted protein product of 963 amino acids. Evaluation of patients revealed no UHX1 mutations using SSCP (10 CSNB1 and 20 XLRP) or deletion screening with cDNA hybridisation (13 CSNB1 and 43 XLRP). Likewise, no aberrations were found in the nearby PCTAIRE1 (PCTK1) gene in 13 CSNB1 and 43 XLRP patients by deletion screening. Thus mutations of UHX1, and probably PCTK1, do not appear to cause common X-linked eye diseases. UHX1's role in patients with mental retardation may be appropriate for further investigations into UHX1 function.

Base Sequence↗