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W Kress

Publications and source records attributed to W Kress.

At least 37 records · Page 2Linked to original sources
PubMed2000

Proximal myotonic myopathy: evidence for anticipation in families with linkage to chromosome 3q.

OBJECTIVE: To investigate anticipation in proximal myotonic myopathy (PROMM). BACKGROUND: PROMM is a recently described autosomal dominantly inherited disorder similar to but distinct from myotonic dystrophy (DM). DM belongs to the group of inherited disorders with anticipation caused by an unstable trinucleotide repeat expansion. In PROMM, no mutation has been identified, although PROMM has recently been mapped to a gene locus on chromosome 3q. METHODS: We investigated 10 German families with the PROMM phenotype and linkage to chromosome 3q. We based our analysis of anticipation on the age of disease onset. Anticipation was assumed if the offspring had first symptoms earlier in life than his or her affected parent. For statistical analysis Independence Estimating Equations (IEE) and a Monte-Carlo bootstrap were used. RESULTS: In 27 affected living parent-offspring pairs from these 10 families, the mean difference of disease onset was 18.8 years with either statistical analysis (p < 10-14 and p < 10-15). The mean disease onset interval in years was greater in father-offspring as compared to the mother-offspring pairs (p < 0.05; IEE). CONCLUSION: Our findings suggest the occurrence of anticipation in parent-offspring pairs from families with the PROMM phenotype and linkage to chromosome 3q. The different disease onset intervals in mother-offspring and father-offspring pairs could indicate a mild parent-of-origin effect. These observations are compatible with the suggestion that PROMM, like DM, may be a trinucleotide repeat associated disorder. In contrast to DM, anticipation in PROMM is milder, a congenital form does not seem to occur, and fertility does not appear to be affected.

Adolescent↗
PubMed2000

MTM1 mutations in X-linked myotubular myopathy.

X-linked myotubular myopathy (XLMTM; MIM# 310400) is a severe congenital muscle disorder caused by mutations in the MTM1 gene. This gene encodes a dual-specificity phosphatase named myotubularin, defining a large gene family highly conserved through evolution (which includes the putative anti-phosphatase Sbf1/hMTMR5). We report 29 mutations in novel cases, including 16 mutations not described before. To date, 198 mutations have been identified in unrelated families, accounting for 133 different disease-associated mutations which are widespread throughout the gene. Most point mutations are truncating, but 26% (35/133) are missense mutations affecting residues conserved in the Drosophila ortholog and in the homologous MTMR1 gene. Three recurrent mutations affect 17% of the patients, and a total of 21 different mutations were found in several independent families. The frequency of female carriers appears higher than expected (only 17% are de novo mutations). While most truncating mutations cause the severe and early lethal phenotype, some missense mutations are associated with milder forms and prolonged survival (up to 54 years).

Alternative Splicing↗
PubMed2000

[Oculopharyngeal muscle dystrophy. Genetic diagnosis in a family in Germany].

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant myopathy with almost benign course. Its clinical features include ptosis, dysphagia, and proximal limb muscle weakness. The OPMD gene has been localized to chromosome 14, causing expansions of GCG triplets. Scattered families with OPMD belonging to different ethnic groups have been described worldwide. We describe one from northern Germany. In genetic diagnosis, expansion of GCG triplets to 11 was observed, which proved that myopathy, which is very rare in Germany.

Blepharoptosis↗
PubMed2000

Hyperparathyroidism in a patient with proximal myotonic myopathy (PROMM).

We describe a 60-year-old woman with progressive proximal leg weakness and dystrophic changes of the quadriceps and the adductor muscles on magnetic resonance imaging. She also suffered from primary hyperparathyroidism. A biopsy of the left deltoid muscle showed vacuoles as an unusual histopathological finding.

Adenosine Triphosphatases↗
PubMed2000

Proof of genetic heterogeneity in the proximal myotonic myopathy syndrome (PROMM) and its relationship to myotonic dystrophy type 2 (DM2).

Recently, myotonic dystrophy type 2 has been described as a separate disease entity that is distinctive from classical Steinert's disease since it lacks a CTG repeat expansion on chromosome 19q. A gene locus for myotonic dystrophy type 2 has been mapped to chromosome 3q. Independently, proximal myotonic myopathy has been recognized as yet another form of a multisystem myotonic disorder. Its relationship to myotonic dystrophy type 2 remains to be clarified. In our linkage study of 17 German proximal myotonic myopathy families nine of them mapped to the myotonic dystrophy type 2 locus (LOD score 18.9). However, two families with a typical proximal myotonic myopathy phenotype were excluded from this locus (LOD score -7.4). These results confirm genetic heterogeneity in the proximal myotonic myopathy syndrome. Furthermore, in the majority of the proximal myotonic myopathy families the disease phenotype may be caused by allelic mutations in the putative myotonic dystrophy type 2 gene.

Chromosomes, Human, Pair 3↗
PubMed2000

Clustering of FGFR2 gene mutations inpatients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses).

A cohort of 36 unrelated German patients with craniosynostosis syndromes of the Crouzon and Pfeiffer type were analyzed for FGFR mutations. Mutations in FGFR2 were identified in 25 Crouzon and 5 Pfeiffer syndrome patients, whereas no sequence alterations were found in the remaining patients, even after screening of the relevant parts of FGFR1, FGFR3, and TWIST. Mutations in FGFR2 clustered at two critical cysteine residues, 278 and 342, which were involved in 18 of 30 cases (60%). These two mutational hot spots, therefore, are prime targets for an efficient mutation-screening strategy. The spectrum of mutations overlapped the two syndromes and thus reflected the phenotypic similarities observed in both patient groups. In 21 families, the origin of the mutation could be traced by analyzing parents and relatives. Eleven mutations arose de novo, indicating a high mutation rate for FGFR2. In the 10 familial cases, the clinical presentation varied considerably within the pedigree, but both syndromes "bred true," i.e., a Pfeiffer syndrome phenotype was never observed in a Crouzon syndrome family and vice versa.

Acrocephalosyndactylia↗
PubMed2000

An unusual FGFR1 mutation (fibroblast growth factor receptor 1 mutation) in a girl with non-syndromic trigonocephaly.

Non-syndromic trigonocephaly is a heterogeneous entity; in most cases the origin is unknown. Rare cases with autosomal dominant and recessive inheritance exist. Here the mutational screening of ten patients in the FGFR1, 2, and 3 genes and the TWIST gene causative of autosomal dominant craniosynostosis syndromes was reported. In one girl an unusual FGFR1 mutation was found.

Adult↗
PubMed1999

Linkage of proximal myotonic myopathy to chromosome 3q.

We performed genetic linkage analysis in nine German proximal myotonic myopathy (PROMM) families using DNA-markers D3S1541 and D3S1589 from the region of the recently discovered gene locus of myotonic dystrophy type 2 (DM2) on chromosome 3q. Two-point analysis supplied an lod score of 5.9. We conclude that a gene causing PROMM is located on chromosome 3q. PROMM and DM2 may be allelic disorders or may be caused by closely linked genes.

Chromosome Mapping↗
PubMed1999

[Current diagnosis in muscular dystrophies. New developments, methods of examination and case examples].

Recent progress in the field of molecular genetics revealed a broader spectrum of dystrophin-related disorders than previously assumed. In addition, the pathogenetic basis of other types of muscular dystrophies could be identified: some autosomal-recessive limb girdle dystrophies are caused by mutations of sarcoglycan genes, others are caused by deficiency of the sarcoplasmatic enzyme calpain-3. Emery-Dreifuss muscular dystrophy is due to the deficiency of the nuclear membrane protein emerin. About 50% of congenital muscular dystrophies are related to mutations of a extracellular matrix protein merosin (alpha-laminin). A series of monoclonal antibodies for immunohistochemistry is now available recognizing many cytoskeletal muscle proteins. In combination with molecular genetics a diagnostic flow chart can be developed which allows a definite diagnosis in most cases. In this review disease entities are illustrated by case reports. We discuss the significance of immunohistochemical and molecular methods for diagnosis.

Adult↗
PubMed1999

Distribution of emerin during the cell cycle.

Human emerin is a nuclear membrane protein that is lost or altered in patients with Emery-Dreifuss muscular dystrophy (EMD). While the protein is expressed in the majority of human tissues analyzed, the pathology predominates in cardiac and skeletal muscles of patients with EMD. Our results show that emerin can be detected by immunocytochemistry and immunoblotting in the nuclear envelope of all vertebrates studied from man to Xenopus. Immunolocalizations and nuclear envelope extraction experiments confirm that emerin possesses properties characteristic for integral membrane proteins of the inner nuclear membrane. Some nuclear envelope proteins are localized also in annulate lamellae (AL), i.e. cytoplasmic flattened membrane cisternae penetrated by pore complexes. To verify whether emerin is contained in these membrane stacks, we have induced the formation of AL by exposure of rat cells (line RV-SMC) to sublethal doses of the antimitotic drug vinblastine sulfate and found that emerin is present in the nuclear envelope, but is absent from AL. In contrast to the homogeneous distribution of emerin in the nuclear envelope of interphase cells, this protein shows a focal accumulation in the nuclear membranes of late telophase cells. During early reassembly of the nuclear envelope at this mitotic stage emerin colocalizes with lamin A/C but not with lamin B and LAP2 proteins. Confocal laser scanning microscopy after double-labeling experiments with emerin and tubulin shows that emerin is concentrated in areas of the mitotic spindle and in the midbody of mitotic cells suggesting a close interaction of these proteins. Our data suggest that emerin participates in the reorganisation of the nuclear envelope at the end of mitosis.

Animals↗
PubMed1999

Allelic heterogeneity of alkaptonuria in Central Europe.

Defects of the homogentisate 1,2 dioxygenase (HGO; E.C. No. 1.13.11.5) have been identified as the molecular cause of alkaptonuria in humans (AKU) and the aku mouse. Here, we report on the genetic basis of 30 AKU patients from Central Europe. In addition to five mutations described previously, we have detected five novel HGO mutations. Recombinant expression of mutated HGO enzymes in E. coli demonstrates the inactivating effect of three of these mutations. A genetic epidemiologic study in Slovakia, the country with the highest incidence of alkaptonuria, demonstrates that two recurrent mutations (c.183-1G > A and Glyl61Arg) are found on more than 50% of AKU chromosomes. An analysis of the allelic association with intragenic DNA markers and of the geographic origins of the AKU chromosomes suggests that several independent founders have contributed to the gene pool, and that subsequent genetic isolation is likely to be responsible for the high prevalence of alkaptonuria in Slovakia.

Alkaptonuria↗
PubMed1999

Interleukin-1 haplotype and periodontal disease progression following therapy.

The purpose of this study was to assess the prognostic value of the IL-1 haplotype on the progression of periodontal disease following therapy. 48 adult patients with untreated periodontitis harboring Actinobacillus actinomycetemcomitans and/or Porphyromonas gingivalis were randomly assigned to receive full-mouth scaling alone (control) or in combination with systemic metronidazole plus amoxicillin and supragingival irrigation with chlorhexidine digluconate (test). All patients received supportive periodontal therapy at 3 to 6 months intervals. In 33 patients, lymphocyte DNA was analyzed for polymorphism in the IL-1A gene at position -889 and IL-1B gene at position +3953. Overall, 16 of 33 patients (7 of 17 test and 9 of 16 control) carried the IL-1 haplotype. 2 years following initial periodontal therapy, no differences in the survival rates of sites or teeth not exhibiting probing attachment loss of 2 mm or more compared to baseline, were found between patients who tested positive (85% sites, 53% teeth) and patients who tested negative (89% sites, 56% teeth) for the IL-1 haplotype. The results indicated that the IL-1 haplotype may be of limited value for the prognosis of periodontal disease progression following non-surgical periodontal therapy.

Adult↗
PubMed1999

Ocular ochronosis in alkaptonuria patients carrying mutations in the homogentisate 1,2-dioxygenase gene.

AIMS: To assess the involvement of the recently identified human homogentisate 1,2-dioxygenase gene (HGO) in alkaptonuria (AKU) in two unrelated patients with ochronosis of the conjunctiva, sclera, and cornea. METHODS: A mutation screen of the entire coding region of the HGO gene was performed using single stranded conformational analysis after polymerase chain reaction with oligonucleotide primers flanking all 14 exons of the HGO gene. Fragments showing aberrant mobility were directly sequenced. RESULTS: Two homozygous missense mutations, L25P and M368V, were identified, each of which leads to the replacement of a highly conserved amino acid in the HGO protein. CONCLUSIONS: The authors describe a novel mutation, L25P, in the German population and bring to 18 the total number of known HGO mutations.

Aged↗
PubMed1999

The novel contiguous gene syndrome of myotubular myopathy (MTM1), male hypogenitalism and deletion in Xq28:report of the first familial case.

Hu et al. (1996) and Laporte et al. (1997) recently proposed a novel contiguous gene syndrome of myotubular myopathy, abnormal male genital development and deletion in Xq28. We studied a family where two male infants, both deceased, had myotubular myopathy and intersexual genitalia. Using FISH we detected in the mother a hemizygous deletion including the myotubularin gene MTM1 and F18 (a gene of yet unknown function). DNA studies with STR-markers (short tandem repeats) within and flanking the deleted segment confirmed the deletion in the family and were used for prenatal diagnosis. Our findings confirm the existence of this novel contiguous gene syndrome and support that the deletion of the F18 gene, or a neighboring gene, may cause ambiguous genitalia or severe hypospadias in males. The mother had low muscle power and marked menstrual irregularities which may indicate that she is a manifesting carrier and that the deletion may include a gene (F18 or other) for gonadal function in females.

Adult↗
PubMed1998

Terminal deletion of the long arm of chromosome 10: a new case with breakpoint in q25.3.

Since the first patient with partial deletion of the long arm of chromosome 10 was described in 1978, another 23 cases have been reported, with the breakpoint ranging from 10q23.3-26.2. To contribute further to the delineation of the monosomy 10qter syndrome, we describe a female child who, at age 3 6/12 years, was diagnosed with a de novo deletion of the long arm of chromosome 10, with a breakpoint in 10q25.3. The phenotypic manifestations in this child are compatible with those of previously reported cases. However, in contrast to most other patients, we found a moderate expression of the syndrome, with no genitourinary or cardiac malformations and with only mild retardation. Based on our observations and those of others, we conclude that a typical craniofacial appearance and varying degrees of psychomotor retardation are always found in patients with 10q- syndrome.

Abnormalities, Multiple↗
PubMed1998

[X-chromosomal recessive spinobulbar muscular atrophy (Kennedy type). Description of a family, clinical aspects, molecular genetics, differential diagnosis and therapy].

The Kennedy-Syndrome is a X-linked recessive bulbospinal muscular atrophy, in some cases associated with endocrinological disturbances such as androgen resistance and diabetes mellitus. The age of onset is usually between 20 and 40. Presenting symptoms are proximal flaccid weakness, fasciculations, cramps or tremor. Disease progression is usually slow and live expectancy is normal. It is important to distinguish the Kennedy-Syndrome from amyotrophic lateral sclerosis, spinal muscular atrophy, muscular dystrophies and other types of motor neuron disease. Kennedy disease is caused by an expanded trinucleotide repeat in the androgen receptor gene. Genetic analysis allows a precise-diagnosis on an individual basis and reliable genetic counselling. An effective medical treatment does not yet exist.

Diagnosis, Differential↗
PubMed1998

Rapid immunoblot and kinase assay tests for a syndromal form of X linked mental retardation: Coffin-Lowry syndrome.

Coffin-Lowry syndrome (CLS) is a syndromal form of X linked mental retardation, in which some associated facial, hand, and skeletal abnormalities are diagnostic features. Accurate diagnosis, critical for genetic counselling, is often difficult, especially in early childhood. We have recently shown that Coffin-Lowry syndrome is caused by mutations in the gene encoding RSK2, a growth factor regulated protein kinase. RSK2 mutations are very heterogeneous and most of them lead to premature termination of translation or to loss of phosphotransferase activity or both. In the present study, we have evaluated immunoblot and RSK2 kinase assays as a rapid and simple diagnostic test for CLS, using cultured lymphoblastoid or fibroblast cell lines. Western blot analysis failed to detect RSK2 in six patients, suggesting the presence of truncated proteins in these patients. This conclusion was confirmed in four patients, in whom the causative mutations, all leading to premature termination of translation, were identified. Of four patients showing a normal amount of RSK2 protein on western blot and tested for RSK2 phosphotransferase activity, one had a dramatically impaired activity. Analysis of the RSK2 cDNA sequence in this patient showed a mutation of a putative phosphorylation site that would be critical for RSK2 activity. Preliminary results show that, at least, the western blot protocol can be successfully applied to lymphocyte protein extracts prepared directly from blood samples. These assays promise to become important diagnostic tools for CLS, particularly with regard to very young patients with no family history of the condition.

Abnormalities, Multiple↗