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Károly Méhes

Publications and source records attributed to Károly Méhes.

14 recordsLinked to original sources
PubMed2006

[Accurate description of the phenotype: the clinician's contribution to the clarification of genotype-phenotype correlations].

Utility of genomics in medical practice highly depends on the knowledge of genotype-phenotype correlations. So far, severity, natural course, drug-sensitivity, etc. belonging to a given mutation have been clarified in only a part of diseases. Concerning such research, the main difficulty is that the objectively determined genotype is often related to the more or less superficially or even subjectively described phenotype. Detailed, accurate, possibly objective recording of the clinical picture and the findings during follow-up by the clinician may make the protracted and heterogeneous collection of data much quicker and more reliable.

Genetics, Medical↗
PubMed2005

Tel Hashomer camptodactyly syndrome: 12-year follow-up of a Hungarian patient and review.

Tel Hashomer camptodactyly syndrome (THCS) was diagnosed in a 4-month-old boy whom we have followed for 12 years. In addition to the characteristic clinical findings, he had preductal coarctation of the aorta, persistent ductus arteriosus, and multiple ventricular septal defects. The electron-microscopic evaluation of his muscle biopsy showed anomalies of the sarcoplasmic reticulum and mitochondria; the organization of the myofibrils was normal. The morphological findings suggested primary or secondary involvement of neuromuscular signal transduction and involvement of mitochondria in the development of the myopathy in this child.

Abnormalities, Multiple↗
PubMed2004

Phenotypic manifestations of the OCTN2 V295X mutation: sudden infant death and carnitine-responsive cardiomyopathy in Roma families.

In two non-consanguineous Hungarian Roma (Gypsy) children who presented with cardiomyopathy and decreased plasma carnitine levels, we identified homozygous deletion of 17081C of the SLC22A5 gene that results in a frameshift at R282D and leads ultimately to a premature stop codon (V295X) in the OCTN2 carnitine transporter. Carnitine treatment resulted in dramatic improvement of the cardiac symptoms, echocardiographic, and EKG findings in both cases. Family investigations revealed four sudden deaths, two of them corresponded to the classic SIDS phenotype. In postmortem tissue specimens available from three of them we could verify the homozygous mutation. In liver tissue reserved from two patients lipid droplet vacuolization could be observed; the lipid vacuoles were located mainly in the peripherolobular regions of the acini. In the heart tissue signs of generalized hypertrophy and lipid vacuoles were seen predominantly in the subendocardial areas in both cases; some aggregates of smaller lipid vacuoles were separated, apparently by membranes. Review of all OCTN2 deficiency cases reported so far revealed that this is the first presentation of histopathology in classic familial sudden infant death syndrome (SIDS) with an established SLC22A5 mutation. In addition to the two affected homozygous cardiomyopathic children and three homozygous sudden death patients, the genetic analysis in 25 relatives showed 14 carriers. The mutant gene derived from five non-consanguineous grandparents, each of them having 6-14 brothers and sisters. This alone suggests a wide ancestral spread of the mutation in certain Roma subpopulations.

Amino Acid Sequence↗
PubMed2004

Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B.

Mosaic variegated aneuploidy is a rare recessive condition characterized by growth retardation, microcephaly, childhood cancer and constitutional mosaicism for chromosomal gains and losses. In five families with mosaic variegated aneuploidy, including two with embryonal rhabdomyosarcoma, we identified truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in the mitotic spindle checkpoint. These data are the first to relate germline mutations in a spindle checkpoint gene with a human disorder and strongly support a causal link between aneuploidy and cancer development.

Abnormalities, Multiple↗
PubMed2004

[Prevention in pediatrics].

Recent achievements in clinical research and progress in molecular biology and genetics have opened new perspectives in maintaining health and preventing disease. Due to its specialty, paediatrics may be particularly effective in utilizing these possibilities. Modern therapeutic procedures may themselves be preventive, in so far as they can ward off complications and late sequelae. In addition to application of new methods, physicians and district nurses dealing with children should go on with unchanged thoroughness in their traditionally successful preventive measures, such as infant care, vaccination, vitamin D prophylaxis, and others. Since health state of infancy and childhood have a significant influence on the quality of life in adulthood, support of paediatric health care and promoting a favourable social background for preventive activities will certainly have long-term advantages.

Child↗
PubMed2004

Clinical manifestations of genetic instability overlap one another.

Cancer syndromes are characteristic associations of specific malignancies with various congenital anomalies. In addition to such diseases, an increased prevalence in general of chromosomal instability, malformations, immunodeficiencies, altered growth and development, and reproductive loss has been observed in both childhood leukemias and solid tumors. The overlap among these congenital disorders suggests their common prenatal, possibly genetic origin and thus the existence of a nonspecific genetic instability leading to various clinical manifestations of disturbances in cell division. Seeking for related features in family members of a patient with malignancy may be of clinical value in detecting predisposition to cancer.

Animals↗
PubMed2003

[Month of birth in childhood acute lymphoblastic leukemia].

INTRODUCTION: An association between date of birth influenced by certain environmental factors (such as virus infections) and malignant diseases has been suggested in some previous papers. AIMS AND METHODS: The authors analyzed the birth dates of 814 children, 0-18 years of age, in whom acute lymphoblastic leukemia was diagnosed in the period between the 1st of January 1988 and 31st of December 2000. RESULTS: No association between month of birth and manifestation of leukemia in Hungarian children could be established. CONCLUSION: The results suggest that this approach was not capable of detecting any obvious prenatal environmental factors, including virus endemics, that could have influenced the appearance of leukemia.

Adolescent↗
PubMed2003

Congenital cataract as the first symptom of a neuromuscular disease caused by a novel single large-scale mitochondrial DNA deletion.

The male proband reported here was born with appropriate anthropometric parameters at term as the second child of healthy nonconsanguineous parents. His only clinical symptom was bilateral congenital cataracts with strabismus at birth, and both lenses were removed surgically at the age of 8 months. The perinatal and infantile period thereafter was clinically uneventful and his psychomotor development appeared almost normal. At the age of 6 years he was hospitalized for slight muscle weakness, minor ptosis, nystagmus and decreased physical activity. Soon after, his general condition worsened, gait ataxia presented, dysphagia and difficulty of speech followed by rapidly progressive generalized ataxia, and myopathy developed. Typical progressive gray matter degeneration with focal necrosis in the basal ganglia characteristic of the Leigh type of neuropathology could be detected by cranial MRI, the muscle histology showed ragged-red fibers. At the age of 7.5 years, unexpected left side hemiparesis with speech disability resembling that seen in MELAS syndrome developed, from which he recovered within 1.5 days. The mtDNA of the patient showed single 6.7 kb large-scale deletion harboring between 7817 and 14 536 bp. This case represents the first report of a verified mtDNA mutation associated with congenital cataracts as the first clinical sign of a later developing progressive neuromuscular disease presented with a combination of Leigh neuropathology, ragged-red fiber histopathology and stroke-like attack.

Cataract↗
PubMed2002

Cleidocranial dysplasia with decreased bone density and biochemical findings of hypophosphatasia.

UNLABELLED: Cleidocranial dysplasia (CCD; MIM 119600) is an autosomal dominant skeletal dysplasia characterised by hypoplastic clavicles, patent fontanelles, short stature, tooth anomalies and other variable skeletal changes. Different mutations of the RUNX2/CBFA1 gene (MIM 600211) have been detected in patients with CCD. We investigated a mother and daughter with features of CCD presenting with reduced plasma alkaline phosphatase activity, increased urinary phosphoethanolamine excretion and decreased bone density. The latter findings were suggestive of hypophophatasia but mutation analysis showed no mutation in the tissue-nonspecific alkaline phosphatase gene (TNSALP; MIM 171760). However, a heterozygous mutation (Arg169Pro caused by nucleotide change 506G > C) was detected in the RUNX2 gene. Metabolic alterations gradually improved in both mother and daughter but bone-specific alkaline phosphatase remained low (less than 30% of normal) and mild phosphoethanolaminuria persisted. Recent studies in the Cbfa1 knock-out mouse showed decreased expression of alkaline phosphatase in differentiating bone. CONCLUSION: we suggest that the observed metabolic alterations are secondary to the RUNX2 gene mutation affecting early bone maturation and turnover. This is the first description of biochemical findings of hypophosphatasia in patients with cleidocranial dysplasia.

Alkaline Phosphatase↗
PubMed2002

Epithelial Ca(2+) channel (ECAC1) in autosomal dominant idiopathic hypercalciuria.

BACKGROUND: The epithelial Ca(2+) channel (ECaC) exhibits the defining properties for being the gatekeeper in 1,25-dihydroxyvitamin D(3)-regulated Ca(2+) (re)absorption. Its recently cloned human orthologue (ECaC1) could, therefore, represent a crucial molecule in human disorders related to Ca(2+)-wasting such as idiopathic hypercalciuria (IH). METHODS: Fifty-seven members of nine families with IH were investigated. Phenotyping was performed by measurements of urinary Ca(2+) excretion, while other underlying disorders were appropriately excluded. Initially, the recently suggested locus for kidney stone-associated hypercalciuria on chromosome 1q23.3-q24 was investigated. Next, direct mutation analysis of all 15 exons of the ECAC1 gene and 2.9 kb upstream from the start codon was performed. hECaC1, heterologously expressed in human embryonic kidney 293 cells, was characterized by patch-clamp analysis. RESULTS: The mode of inheritance in the studied pedigrees is consistent with an autosomal dominant trait. Haplotype analysis did not implicate a role of the locus on chromosome 1. The coding sequence of the ECAC1 gene was not different between the affected and the non-affected family members. In the 5'-flanking region, three single nucleotide polymorphisms were encountered, but these polymorphisms were observed regardless of the affection status of the screened family members. Patch-clamp analysis of hECaC1 was performed as the putative pore region contains four non-conserved amino acid substitutions compared with the other species. This analysis revealed the distinctive properties of ECaC, including a high Ca(2+) selectivity, inward rectification, and Ca(2+)-dependent inactivation. CONCLUSION: These results do not support a primary role for hECaC1 in IH in nine affected families. Because of the heterogeneity of the disease, however, the involvement of ECaC1 in other subtypes of IH cannot be excluded and needs further investigation. The electrophysiological properties of hECaC1 further substantiate its prime role in Ca(2+) (re)absorption.

Adolescent↗
PubMed2002

Gastrointestinal malformations, associated congenital abnormalities, and intrauterine growth.

BACKGROUND: In contrast with other malformations, congenital anomalies of the gastrointestinal tract have been scarcely investigated. METHODS: The prevalence of gastrointestinal malformations with special reference to associated disorders and intrauterine growth was retrospectively analyzed in the newborn infants admitted to the Neonatal Intensive Care Unit of the Department of Pediatrics, University of Pécs, Hungary, in the 14-year period between 1987 and 2000. RESULTS: Of 4,241 neonates with gastrointestinal malformations, 241 (5.68%) had a total of 304 malformations (excluding Hirschsprung disease). In 133 patients, the gastrointestinal anomalies were observed as one of multiple malformations; a specific syndrome or association was diagnosed in 36 cases. Skeletal disorders were the most frequently associated anomalies. Intrauterine growth retardation was found in a large number of patients with both isolated and multiple gastrointestinal malformations (38.9% and 30.8%, respectively). CONCLUSIONS: Gastrointestinal malformations often are complicated by skeletal anomalies and intrauterine growth retardation. The association among these disorders requires further investigation. However, from a practical point of view, this association should be considered in treating affected patients.

Birth Weight↗
PubMedDate not supplied

Association of wilms tumor with spinal dysraphism.

Previous data suggested an association of vertebral anomalies with Wilms tumor. At the same time, vertebral midline fusion defects are often indicated by dermal anomalies over the spine. In the present study the prevalence of both occult spina bifida and cutaneous signs of spinal dysraphism was significantly higher in 50 Wilms patients than in 180 control children (18.0 versus 4.4%, p <.01, and 35.9 versus 17.5%, p <.02, respectively). Family investigations are needed to answer the question whether signs of spinal dysraphism in parents and sibs of patients may be regarded as indicators of an increased risk of Wilms tumor in the family.

Child↗