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Biomedical subjects

J U Walther

Publications and source records attributed to J U Walther.

At least 19 recordsLinked to original sources
PubMed1994

Tetrasomy 21 pter-->q22.1 and Down syndrome: molecular definition of the region.

Down syndrome is usually caused by complete trisomy 21. Rarely, it is due to partial trisomy of the segment 21q22. We report on a 33-month-old girl with tetrasomy 21 pter-->q22.1 resulting from an extra chromosome idic(21)(q22.1). She has craniofacial traits typical of Down syndrome, including brachycephaly, third fontanel, upward slanting palpebral fissures, round face, and protruding tongue. Speech development is quite delayed whereas motor development is only mildly retarded. The molecular content of the extra isodicentric chromosome was defined by molecular genetic investigations using 13 single copy probes unique to chromosome 21, and SOD1 expression studies. The child was found to have 4 copies of the region defined by D21S16 (21cen) through D21S93 on 21q22.1 and two copies of the remaining region defined by SOD1-->D21S55-->D21S123. In view of the recent assignment of Down syndrome facial characters to the 21q22 region, defined in part by D21S55, it is significant that this child shows a subset of Down syndrome facial manifestations, without duplication of this region. These results suggest that genes contributing to the facial and some of the hand manifestations of Down syndrome also exist in the chromosomal region proximal to D21S55 in band 21q22.1.

Blotting, Southern↗
PubMed1993

[Incontinentia pigmenti in a male patient].

Incontinentia pigmenti (Bloch-Sulzberger syndrome) is a rare genetic disorder usually affecting females. Familial cases show an X-linked dominant inheritance with male lethality. The typical skin manifestations occur in several stages and can be associated with various extracutaneous anomalies. We report on a 10-month-old male patient with incontinentia pigmenti (IP) and a normal male karyotype. Besides the typical cutaneous lesions no other signs have been found so far. IP in male patients can be explained by the presence of Klinefelter syndrome, by the half-chromatid mutation model, or by an early somatic mutation. On the basis of this case report we discuss the clinical findings in and the genetics of IP.

Biopsy↗
PubMed1993

Detection and clinical relevance of genetic abnormalities in pediatric acute lymphoblastic leukemia: a comparison between cytogenetic and polymerase chain reaction analyses.

The E2A/PBX1 and the BCR/ABL fusion genes result from the t(1;19)(q23;p13) and the t(9;22)(q34;q11), respectively, and encode oncoproteins which are thought to play an important role in the development of acute lymphoblastic leukemia (ALL) subtypes associated with adverse prognosis. The use of the polymerase chain reaction (PCR) for the detection of these genetic rearrangements may offer advantages over cytogenetic techniques which are often unsatisfactory in patients with ALL and, furthermore, provide a useful tool for monitoring of residual disease. However, it has not yet been evaluated whether the employment of PCR at the time of diagnosis improves the detection rate of these clinically relevant genetic anomalies. We have developed a multiprimer-PCR protocol which facilitates the detection of each of the four chimeric E2A/PBX1 and BCR/ABL mRNAs in a single reaction. This protocol was used for the evaluation of bone-marrow or blood samples from 251 children with ALL in whom cytogenetic analyses had been performed. Of the 251 patients, 221 had a B-cell precursor immunophenotype. In this group, 21 patients (9.5%) carrying the E2A/PBX1 rearrangement and three patients (1.4%) with BCR/ABL transcripts were detected by PCR. Twelve of these cases had escaped the detection by conventional cytogenetic analysis. In two of 12 patients with a typical t(1;19)(q23;p13), no E2A/PBX1 transcripts were identified by PCR, thus suggesting the presence of different molecular rearrangements. Residual leukemic cells were detected by PCR in five of eight patients who were followed during complete clinical remission. The frontline use of PCR has an important impact on the timely diagnosis, therapeutic decisions, and monitoring of high-risk patients with B-cell precursor leukemia who carry the E2A/PBX1 or BCR/ABL fusion genes.

Adolescent↗
PubMed1992

[Human genetics and transplantation].

Transplantations represent an important element of treatment in end-stage chronic disease both inborn (mostly genetic) and acquired (degenerative, neoplastic). They are supposed to establish durable coexistence of cells with different genetic origin (in most cases). This union is contradictory to immunological properties of the tissues involved and can only succeed in case of sufficient histocompatibility to be identified by the diagnostic tests of immunogenetics. This review discusses the current approach used in choosing the most appropriate donor for an individual patient, and in monitoring the maintenance of "chimerism" established by the transplantation focussing on bone marrow transplantation. Initially a general outline of indications for organ transplantation is given with emphasis laid on genetic disorders as the outlook of conservative treatments in inborn diseases is generally very poor.

Bone Marrow Transplantation↗
PubMed1992

[Juvenile chronic leukemia and chronic myelomonocytic leukemia. Experiences with bone marrow transplantation in childhood in 5 cases].

Chronic leukemias of early childhood (JCML/CMML) are rare malignant diseases for which effective regimens of chemotherapy have not been established. However, some of these patients may be cured by BMT. We report on 4 children with JCML and one child with CMML undergoing BMT from HLA-identical siblings and from matched unrelated donors. 3 of 5 patients are disease-free 9 to 37 months post BMT. According to our observations an effective reduction of blastic cells before BMT seems to be necessary for a sustained remission of these diseases. This reduction can be reached by intensive chemotherapy and by splenectomy before BMT. Moreover, we stress the need for total body irradiation (TBI) during BMT in order to eradicate residual malignant cells.

Blood Cell Count↗
PubMed1990

Dubowitz syndrome: atopic dermatitis, low birth weight dwarfism and facial dysmorphism.

The association of low birth weight dwarfism, distinct facial dysmorphism and eczematous skin lesions has been described repeatedly since the first description by Dubowitz in 1965. The way of inheritance seems to be in some cases autosomal recessive. Because of the rarity of this entity, another case is reported showing an additional preauricular fistula.

Child, Preschool↗
PubMed1990

[Concordant myaplasia of the thoracic wall in monozygotic twins (Poland anomaly)].

A set of monozygotic twins affected with unilateral shoulder girdle muscle aplasia is reported. One twin showed Poland-like aplasia of the pectoralis but without the ipsilateral dysmelia, the other aplasia of dorsal spinothoracic muscles. The controversy about exogenous or genetic causes of the Poland anomaly and the whole spectrum of shoulder myaplasia may be solved assuming a multifactorial origin. The striking sex distribution and the continuous range of symptoms observed are in keeping with this hypothesis.

Diseases in Twins↗
PubMed1990

[Genetics in child and adolescent psychiatry].

UNLABELLED: It is agreed, that all phaenomena of human life are under some genetic control, even the emotional and mental elements of the personality. However, the practical application of clinical genetics to classifying and diagnosing psychiatric illness in children is limited to certain patients. These may be classified according to criteria of history and clinical findings. a) HISTORY: Pedigree information about familiarity; miscarriages indicating aneuploidy; progressive course of illness. table; (see text) b) Clinical: (1) Physical signs (permanent morphological abnormalities, esp. symmetrical), whether present at birth or later; disturbance of more than one biological system; temporal and functional anomalies of puberty; presence of convulsive symptoms. (2) Mental retardation and abnormalities of behaviour and experience of the self: exclusion of the fra-X-syndrome is indicated in young children with autism and in hyperkinetic patients. In this category the gonosomal aberrations should also be considered particularly, when hormonal changes are present.

Child↗
PubMed1984

Deficiency of plasmalogens in the cerebro-hepato-renal (Zellweger) syndrome.

We have analyzed the phospholipid composition of various organs of patients with the cerebro-hepato-renal (Zellweger) syndrome. The phospholipid composition of tissues from controls and patients was very similar except for their plasmalogen contents. In controls about 50% of the phosphatidylethanolamine fraction of brain, heart, kidney and skeletal muscle and about 10% of that fraction in control liver tissue was found to consist of plasmalogen. In control heart muscle, but not in other control tissues about 25% of the phosphatidylcholine fraction consist of plasmalogens. In contrast, plasmalogens were nearly absent in the corresponding tissues of Zellweger patients. The amount of phosphatidylethanolamine plasmalogens in both erythrocytes and fibroblasts of Zellweger patients is lowered significantly compared to control erythrocytes and control fibroblasts respectively, although this reduction is not as dramatic as in brain, heart, kidney, skeletal muscle and liver of patients. Phosphatidylcholine-plasmalogens are only present in low amounts in both controls, heterozygotes and patients. In recent years considerable evidence has accumulated to show that peroxisomes are involved in cellular lipid metabolism. Notably, the key enzymes of ether lipid (plasmalogen) biosynthesis in rodents were recently found to be located in peroxisomes. Since electronmicroscopic studies have shown that peroxisomes are absent in liver and kidney of patients with the cerebro-hepato-renal syndrome, our results suggest that an inability to integrate these key enzymes in a functional peroxisome leads to a severe disturbance in plasmalogen biosynthesis. We propose that the multiple clinical and biochemical defects in Zellweger patients are secondary to a deficiency in peroxisomal function.

Brain Diseases↗
PubMed1984

Mitochondrial myopathy with loosely coupled oxidative phosphorylation in a case of Zellweger syndrome. A cytochemical-ultrastructural study.

A newborn female, the second child of consanguineous parents, exhibited general muscle hypotonia, apathy, hepatomegaly and failure to thrive from birth and signs of craniofacial dysmorphia were present. Pipecolic and trihydroxicoprostanoic acid were excreted in the urine and serum transferrin, ferritin and iron were markedly elevated. At the age of 7 weeks the baby died of respiratory insufficiency. Besides malformations of the brain, renal cysts, liver damage with hypoplastic intrahepatic bile ducts and cholestasis, increased storage of iron and cytochemically proven deficiency of peroxisomes in liver and kidney, morphological studied provided evidence of a mitochondrial myopathy in striated muscle with the accumulation of enlarged bizarre mitochondria, showing only minor structural abnormalities. No defects of NADH-reductase, succinate-dehydrogenase or cytochrome-c-oxidase were demonstrated histochemically. Cytochemical-ultrastructural investigation of mitochondrial ATPase revealed activation of the ATP-synthesising enzyme even before the addition of an uncoupler, this indicating loosely coupled oxidative phosphorylation. In addition a high rate of subcellular autophagy with segregation of mitochondria and focal loss of fibrils was present. Muscle damage in Zellweger syndrome appears to be the consequence of complex, interacting metabolic processes. The mitochondrial myopathy thereby induced allows a better understanding of general muscle hypotonia, one of the leading symptoms of this disorder.

Adenosine Triphosphatases↗
PubMed1984

[Prevention of lip-maxilla-palate clefts].

Cheilognathopalatoschisis is among the common isolated congenital malformations. Its occurrence is more frequent than random incidence would be, with high familial incidence. Preventive attempts have been guided by the concept that nutritive factors are involved in the realisation of these inhibitory malformations. A multivitamin substitution course initiated even before conception was found to be correlated with a significant reduction of recurrence rates in several studies. The statistical and practical implications and problems are discussed. This treatment can be recommended as an individual preventive measure in case of pregnancies with risk of cheilognathopalatoschisis, but it will not be helpful in familial incidence of median cleft palate.

Cleft Lip↗
PubMed1984

Hereditary persistence of fetal haemoglobin (HPFH) in conjunction with a chromosomal translocation involving the haemoglobin beta locus.

An HPFH syndrome was found in a woman and her daughter who also carry a 'balanced' cyclic translocation of chromosome segments involving four chromosomes, with one break point located in the region of the Hb beta locus. This HPFH is characterized by 5% and 8% Hb F in peripheral blood, uneven distribution of Hb F in the red cells, and a G gamma/G gamma + A gamma ratio of 0.4. The mapping of the non alpha gene cluster shows no detectable deletion in the entire gamma-delta-beta-globin gene region.

Adult↗
PubMed1983

Specific translocation t(4;11) in an infant with acute lymphoblastic leukaemia of null cell type.

A case of acute lymphoblastic leukaemia of null cell type in infancy showed the specific reciprocal translocation t(4;11) (q21;q23) reported 16 times so far in the world literature. The proportions of abnormal and normal metaphases throughout the course of the illness correlated well with the clinical picture, but even during the short term remission metaphases expressing the translocation were still identifiable in appreciable numbers. Comparison between cytogenetic analyses of cultured and native bone marrow, PHA-stimulated and non-stimulated peripheral blood demonstrated the gradual conquest of the periphery by the abnormal clone. The importance of chromosomal changes and their interpretation for diagnosis, classification and prognostic judgment in haemotologic neoplasms is discussed in the light of the reported case.

Bone Marrow Cells↗
PubMed1982

The developmental change in the G gamma and A gamma globin. Proportions in hemoglobin F.

The proportions of G gamma and A gamma globins in hemoglobin F were determined in fetuses around the 20th week of gestation, newborns, and children 3 weeks to 5 months of age. In the last group, the G gamma/G gamma + A gamma ratio decreased continously; there was a good correlation between the decline of G gamma with respect to total gamma and the decline of Hb F (r = 0.88). In contrast, there was virtually no difference in the gamma globin composition of Hb F between the fetuses and the newborns, i.e. in late pregnancy, the decrease in the synthesis of both gamma globins appears to be proportionate. The G gamma and A gamma globin genes may be inactivated in a sigmoidal fashion with time, thus producing a G gamma/G gamma + A gamma ratio which at first changes only slightly and then declines linearily.

Age Factors↗