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B Wittwer

Publications and source records attributed to B Wittwer.

At least 19 recordsLinked to original sources
PubMed2000

Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III.

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.

Adolescent↗
PubMed2000

Clinical presentation and mutation identification in the NBS1 gene in a boy with Nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder which belongs to the group of inherited chromosomal instability syndromes. The clinical characteristics include severe microcephaly, a dysmorphic facies, and immunodeficiency with predisposition to malignancies. While the cellular characteristics of ataxia teleangiectasia (AT) and NBS are similar, the clinical findings are quite distinct. NBS patients show characteristic microcephaly, which is rare in association with AT and they do not develop ataxia and teleangiectasia. Recently, the gene mutated in NBS has been identified. Here we report a 5-year-old Bosnian boy with severe microcephaly. Because of multiple structural aberrations involving chromosomes 7 and 14 typical for AT (MIM 208900) and NBS (MIM 251260), AT was diagnosed. We suggested the diagnosis of NBS because of the boy's remarkable microcephaly, his facial appearance, and the absence of ataxia and teleangiectasia. DNA analysis was performed and revealed that the boy is homozygous for the major mutation (657de15) in the NBS1 gene. This finding confirms the diagnosis of NBS in our patient and offers the possibility to perform a most reliable prenatal diagnosis in a further pregnancy.

Adult↗
PubMed1998

Submicroscopic deletion in 14q32.3 through a de novo tandem translocation between 14q and 21p.

We describe a male child with craniofacial anomalies, postnatal onset growth retardation, microcephaly, multiple minor anomalies, hearing loss, and moderate delay of mental and statomotor development. He carries a previously undescribed tandem translocation between the long arm of chromosome 14 and the short arm of chromosome 21 that arose de novo. As proven by fluorescence in situ hybridization a microdeletion not detectable with high-resolution G-banding occured in 14q32.3, the terminal band on the long arm of chromosome 14. The resulting phenotype includes most abnormalities encountered in patients with terminal 14q32.3 deletions but in addition includes some characteristics of the ring chromosome 14 syndrome.

Abnormalities, Multiple↗
PubMed1998

Opitz G/BBB syndrome in Xp22: mutations in the MID1 gene cluster in the carboxy-terminal domain.

The MID1 gene in Xp22 codes for a novel member of proteins containing a RING finger, B-box, coiled-coil and a conserved C-terminal domain. Initially, three mutations in the C-terminal region were found in patients with Opitz G/BBB syndrome, a defect of midline development. Here we have determined the complete gene structure of the MID1 gene and have analyzed all nine exons for mutations in a set of 40 unrelated Opitz G/BBB patients. We now report six additional mutations all clustered in the carboxy-terminal domain of the MID1 protein. These data suggest that this conserved domain of the B-box proteins may play a fundamental role in the pathogenesis of Opitz syndrome and in morphogenetic events at the midline during blastogenesis.

Abnormalities, Multiple↗
PubMed1996

New X-linked mental retardation syndrome with the gene mapped tentatively in Xp22.3.

X-linked mental retardation (XLMR) is genetically heterogeneous and clinically variable. We describe a new XLMR syndrome of severe mental retardation and multiple congenital anomalies. Two sisters have (with 3 different partners) 3 severely handicapped sons. In 2 cases, oligohydramnios and intrauterine growth retardation were noted. Common anomalies included a square-shaped face, high and broad forehead, frontal bossing, downward slant of palpebral fissures, hypertelorism, epicanthic folds, long philtrum, thin upper lip, and apparently low-set ears. One boy has bilateral microphthalmos and sclerocornea, and his cousin has atrophy of the optic nerve. All 3 patients are blind and have profound statomotor and mental retardation, seizures, and a grossly abnormal electroencephalographic pattern. Additional findings are short stature, delayed bone maturation, hydronephrosis, vesicorenal reflux, cryptorchidism, clinodactyly of the 5th fingers, and transverse palmar creases. The karyotype is normal (46,XY). Segregation analysis showed perfect coinheritance between the clinical phenotype and alleles at several loci in Xp22.3, whereas recombinants were identified with marker loci from Xp22.2-qter. Analysis of multiple informative meioses suggests that the disease locus maps in Xp22.3 distal to DXS16.

Abnormalities, Multiple↗
PubMed1996

A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).

X-linked retinitis pigmentosa (xlRP) is a severe progressive retinal degeneration which affects about 1 in 25,000 of the population. The most common form of xlRP, RP3, has been localised to the interval between CYBB and OTC in Xp21.1 by linkage analysis and deletion mapping. Identification of microdeletions within this region has now led to the positional cloning of a gene, RPGR, that spans 60 kg of genomic DNA and is ubiquitously expressed. The predicted 90 kD protein contains in its N-terminal half a tandem repeat structure highly similar to RCC1 (regulator of chromosome condensation), suggesting an interaction with a small GTPase. The C-terminal half contains a domain, rich in acidic residues, and ends in a potential isoprenylation anchorage site. The two intragenic deletions, two nonsense and three missense mutations within conserved domains provide evidence that RPGR (retinitis pigmentosa GTPase regulator) is the RP3 gene.

Amino Acid Sequence↗
PubMed1995

A gene (SRPX) encoding a sushi-repeat-containing protein is deleted in patients with X-linked retinitis pigmentosa.

X-linked retinitis pigmentosa (XLRP) is characterized by retinal degeneration with night blindness and progressive reduction of the visual fields. By linkage and deletion analysis a gene locus (RP3) has been mapped to the short arm of the X chromosome between the genes CYBB and OTC. Analysis of transcript in this region has revealed a gene which is abundantly expressed in human retina and encodes a putative membrane protein with significant homologies to short consensus repeat (SCR/sushi) domains known from selections and complement proteins. The gene termed SRPX (sushi-repeat-containing protein, x chromosome) is deleted in an RP patient who also suffers from chronic granulomatous disease and McLeod syndrome. A 75 kb deletion removing exon 1 of the gene was also found in two brothers of a second XLRP family. However, no further functionally significant mutations were detected by SSCP screening of all 10 exons in 34 unrelated XLRP patients nor by full length RT-PCR sequencing in two RP3 families. The role of this highly conserved retinal gene in the pathogenesis of RP therefore remains to be determined.

Adult↗
PubMed1987

[Strategic cytogenetic aids in oncologic diagnosis and individual therapy control].

The main cytogenetic markers of haemoblastoses and other myelo- and lymphoproliferative disorders as well as an oncologically relevant gene map of the human chromosomes were demonstrated taking as a basis own data and corresponding literature. We have tried to describe the current prognostic value of several karyotypic traits and trends for the use of clinicians, especially for oncologists, from the cytogenetic point of view. We particularly consider the dynamics and the development, the competition between various cell-lines of the bone-marrow with different changes of the karyotypes. Further attempts to a clear understanding of the nature and the significance of clonal chromosome changes in haemoblastoses and other tumours as well as of the risk of neoplastic development determined by distinct chromosomal abnormalities should take into consideration the molecular mechanisms of translocation and also the consequences of gene dosis, such as of immunologic systems. At present cytogenetic tumour markers seem to be a strategic aid for diagnosis and prognosis as well as for the understanding of the mechanisms, initiating the chromosome aberrations and leading to further changes during the development of the tumour.

Chromosome Aberrations↗
PubMed1979

[Length measurements by rocking-plate micrometry at the fundus of the human eye (author's transl)].

An additional unit which can be used for length measurements at the fundus of the human eye is described for the ophthalmoscope. The principle of measurement is based on optical displacement of the measuring object to itself. The optical displacement of picture points is made possible by the use of a tilting flat glass plate in the intermediate image plane of the eyepiece. The relation between the optical displacement of picture points and the measuring movement is sufficiently linear for the described device.

Fundus Oculi↗
PubMed1978

[Self-treatment among employees of the Swiss railroad and postal systems].

In this paper some initial results of a study of self-treatment in case of light illness are reported. The average number of reported measures taken is 3,5 in general infections and infections of the respiratory tract, 2,6 in digestive disorders, and 2,5 in disorders of the musculo-skeletal system. In all three groups of disorders, the most frequent single measures was bed rest, the second most frequent was measuring body temperature in the first diagnostic group, drinking tea in the second, and massage in the third. In the first diagnostic group, an average of 2,2 pharmacologic agents are taken, in the second 1,1, and in the third 1,3. Analgesic drugs play an important role in all three groups, pointing to the primordial role of pain relief in self-medication. 84,5% of the interviewed sample indicate use of folk medicines. 90% of the applied drugs come from the stock of the home pharmacy.

Adult↗