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T Mazurczak

Publications and source records attributed to T Mazurczak.

At least 19 recordsLinked to original sources
PubMed2001

Clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18.

We report the results of detailed clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18. Classical cytogenetics and fluorescence in situ hybridization (FISH) analysis with the chromosome 18 painting probe identified five non-mosaic and two complex mosaic 46,XX,dup(18)(p11.2)/47,XX,dup(18)(p11.2),+r(18) and 46,XX,dup(18)(p11.32)/47,XX,dup(18)(p11.32),+r(18) cases. FISH analysis was performed for precise characterization of the chromosome 18 breakpoints using chromosome 18-specific short-arm paint, centromeric, subtelomeric, and a panel of fifteen Alu- and DOP-PCR YAC probes. The breakpoints were assessed with an average resolution of approximately 2.2 Mb. In all r(18) chromosomes, the 18q terminal deletions ranging from 18q21.2 to 18q22.3 ( approximately 35 and 9 Mb, respectively) were found, whereas only in four cases could the loss of 18p material be demonstrated. In two cases the dup(18) chromosomes were identified as inv dup(18)(qter-->p11.32::q21.3-->qter) and inv dup(18)(qter-->p11.32::p11.32-->p11.1: :q21.3-->qter)pat, with no evidence of an 18p deletion. A novel inter-intrachromatid mechanism of formation of duplications and ring chromosomes is proposed. Although the effect of "ring instability syndrome" cannot be excluded, the phenotypes of our patients with characteristic features of 18q- and 18p- syndromes are compared and correlated with the analyzed genotypes. It has been observed that a short neck with absence of cardiac anomalies may be related to the deletion of the 18p material from the r(18) chromosome.

Abnormalities, Multiple↗
PubMed2001

Cytogenetic and molecular characterization of two isodicentric Y chromosomes.

We report the results of detailed molecular-cytogenetic studies of two isodicentric Y [idic(Y)] chromosomes identified in patients with complex mosaic karyotypes. We used fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) to determine the structure and genetic content of the abnormal chromosomes. In the first patient, classical cytogenetics and FISH analysis with Y chromosome-specific probes showed in peripheral blood lymphocytes a karyotype with 4 cell lines: 45,X[128]/46,X,+idic(Y)(p11.32)[65]/47,XY,+idic(Y)(p11.32)[2]/47,X,+2idic(Y)(p11.32)[1]. No Y chromosome material was found in the removed gonads. For precise characterization of the Yp breakpoint, FISH and fiberFISH analysis, using a telomeric probe and a panel of cosmid probes from the pseudoautosomal region PAR1, was performed. The results showed that the breakpoint maps approximately 1,000 Kb from Ypter. The second idic(Y) chromosome was found in a boy with mild mental retardation, craniofacial anomalies, and the karyotype in lymphocytes 47,X,+idic(Y)(q11.23),+i(Y)(p10)[77]/46,X,+i(Y)(p10)[23]. To our knowledge, such an association has not been previously described. FISH and PCR analysis indicated the presence of at least two copies of the SRY gene in all analyzed cells. Using 17 PCR primers, the Yq breakpoint was shown to map between sY123 (DYS214) and sY121 (DYS212) loci in interval 5O in AZFb region. Possible mechanisms of formation of abnormal Y chromosomes and karyotype-phenotype correlations are discussed.

Abnormalities, Multiple↗
PubMed2001

[Results of 1043 prenatal cytogenetic studies: retrospective study in the context of applicability of interphase FISH in prenatal diagnosis]].

OBJECTIVES: The risk of aneuploidy in a fetus is the main reason for referral in approximately 80% of prenatal studies. Recently, a new method for rapid detection of the most frequent aneuploidies affecting chromosomes 13, 18, 21, X and Y has been developed. Fluorescence in situ hybridisation (FISH) on uncultured fetal cells with probes specific for these chromosomes has been described which enables diagnosing aneuploidies within 24 to 48 hours. The purpose of the study was evaluation of clinical utility of this new method in prenatal diagnostics. MATERIALS AND METHODS: Retrospective analysis of the results of 1043 prenatal cytogenetic studies performed with conventional banding methods was done. Number and type of chromosomal abnormalities found in different categories of indications with special emphasis on aberrations undetectable by FISH were analysed. RESULTS: Chromosomal aberrations were found in 4.7% studies. The frequency of aneuploidies was 1.8% accounting for 35.8% of all diagnosed chromosomal abnormalities. In the group of 854 studies performed for elevated risk of aneuploidy it accounted for 60.7% (17/28) abnormalities. All other aberrations could not be detected by FISH with probes for most frequent aneuploidies. Among them, there were 6 unbalanced: del (8) and pseudic (15) with known abnormal phenotype and 4 marker chromosomes with unknown clinical consequences. Three other abnormalities were balanced but familial origin of them was documented. CONCLUSIONS: A karyotype using classical banding methods should be performed whatever the indication of prenatal study is. It is the only fully informative method able to detect all chromosomal abnormalities. Interphase FISH assay must be considered as a complementary procedure to fetal karyotype analysis as it is designed only for aneuploidy identification. However it may be a very useful method for rapid diagnosis in specific clinical conditions especially in the cases of high risk of aneuploidy.

Adult↗
PubMed2000

Identification of supernumerary marker chromosomes derived from chromosomes 5, 6, 19, and 20 using FISH.

A large number of cases with supernumerary marker chromosomes (SMCs) should be compared to achieve a better delineation of karyotype-phenotype correlations. Here we present four phenotypically abnormal patients with autosomal marker chromosomes analysed by fluorescence in situ hybridisation using centromeric, telomeric, and unique sequence probes, as well as forward and reverse painting. We also report the first case, to the best of our knowledge, of an SMC derived from chromosome 5. Furthermore, a marker chromosome 20 in a patient with sex differentiation abnormalities, a double mar(6) in a boy with psychomotor retardation, and the association of r(19) with dup(21q21.2q22.12) are described. Although the mar(6) was very small, the presence of euchromatin was shown, suggesting that the partial trisomy of pericentric region derived sequences is implicated in the aetiology of the abnormal phenotypes.

Adolescent↗
PubMed1999

High rate of mosaicism in tuberous sclerosis complex.

Six families with mosaicism are identified in a series of 62 unrelated families with a mutation in one of the two tuberous sclerosis complex (TSC) genes, TSC1 or TSC2. In five families, somatic mosaicism was present in a mildly affected parent of an index patient. In one family with clinically unaffected parents, gonadal mosaicism was detected after TSC was found in three children. The detection of mosaicism has consequences for genetic counseling of the families involved, as changed risks apply to individuals with mosaicism, both siblings and parents. Clinical investigation of parents of patients with seemingly sporadic mutations is essential to determine their residual chance of gonadal and/or somatic mosaicism, unless a mosaic pattern is detected in the index patient, proving a de novo event. In our data set, the exclusion of signs of TSC in the parents of a patient with TSC reduced the chance of one of the parents to be a (mosaic) mutation carrier from 10% to 2%. In the five families with somatic mosaicism, the parent was given the diagnosis after the diagnosis was made in the child.

Base Sequence↗
PubMed1997

Familial four breakpoint complex chromosomal rearrangement as a cause of monosomy 9p22-->pter and trisomy 10p11.2-->pter and 11q21 analysed by dual and triple colour FISH.

A familial four breakpoint complex chromosomal rearrangement involving chromosomes 9, 10, and 11 was ascertained through a child with dysmorphic features, hypertrophic cardiomyopathy, and hypotonia. A cryptic insertion, invisible in G banded chromosomes was identified by fluorescence in situ hybridisation (FISH) using chromosome specific libraries. Possible mechanisms of its formation as well as karyotype-phenotype correlation are discussed.

Adult↗
PubMed1996

Frequency of Fra X syndrome among institutionalized mentally retarded males in Poland.

Results of cytogenetic studies, performed in a group of 201 institutionalized mentally retarded males, are presented. At least two cytogenetic methods for eliciting the Xq27.3 fragile site, recommended by the Fourth International Workshop on the Fra X Syndrome were used. A subgroup of 67 out of 201 studied males was also examined using molecular methods. In 6 (2.9%) males fra X syndrome was diagnosed. All cytogenetic positive results were confirmed by molecular analysis. Five patients had full expansion CGG repeats and one had both premutation and full mutation. Postulated frequency of fra X syndrome in Polish population being 0.2-0.4/1,000 males seems to be lower than it could be expected on the basis of previous literature data.

Fragile X Syndrome↗
PubMed1996

Molecular and clinical studies of Polish patients with Prader-Willi syndrome.

A group of 30 patients clinically described as having the Prader-Willi Syndrome (PWS) were studied using microsatellites from 15q11-13 and methylation analysis with probe PW71B (D15S63). The patients were categorized according to clinical symptoms. 80% of all patients were informative using molecular and cytogenetic methods. Among 8 patients with an atypical PWS phenotype, 2 showed uniparental disomy, and 2 had a mosaic deletion for 15q. The last 4 atypical and 2 typical patients had neither molecular defects confirmed by microsatellite analysis nor a parent-of-origin-specific methylation pattern for PWS. Our results confirm that methylation pattern analysis provides an additional and alternative microsatellite analysis to diagnose PWS.

Adolescent↗
PubMed1996

Analysis of unstable DNA sequence in FMR1 gene in Polish families with fragile X syndrome.

The unstable DNA sequence in the FMR1 gene was analyzed in 85 individuals from Polish families with fragile X syndrome in order to characterize mutations responsible for the disease in Poland. In all affected individuals classified on the basis of clinical features and expression of the fragile site at X(q27.3) a large expansion of the unstable sequence (full mutation) was detected. About 5% (2 of 43) of individuals with full mutation did not express the fragile site. Among normal alleles, ranging in size from 20 to 41 CGG repeats, allele with 29 repeats was the most frequent (37%). Transmission of premutated and fully mutated alleles to the offspring was always associated with size increase. No change in repeat number was found when normal alleles were transmitted.

Alleles↗
PubMed1996

[Clinical genetics problems in pediatric practice].

A general approach to genetic problems in paediatrics has been presented. The rapid developments in molecular genetic techniques have made it clear that genetic concepts are important in all areas of medicine. Because the majority of genetic disorders are diagnosed at birth or during the first years of life, "thinking genetically" has become an important element of paediatric education. Types of genetic disorders and priorities in diagnostic procedures are presented. Diagnostic possibilities based on DNA analysis in an increasing number of disorders as well as treatment and prevention problems are discussed.

Genetic Counseling↗
PubMed1996

[Inter-generational transmission of mutations responsible for fragile X syndrome].

Inter-generational transmission of normal and mutated (CGG)n sequences in the FMR1 gene was studied in 17 Polish fragile X families. All normal alleles were stable when transmitted to the progeny. Twenty-five of the 26 transmitted maternal premutations expanded to full mutation level. No correlation between the number of CGG repeats in the maternal premutation and the size of the mutation in the offspring was found. Analysis of the mutation size in siblings revealed that the length of full mutations is sex-dependent. The average length of the (CGG)n sequence in sons of fragile X female carriers was larger than in daughters.

Alleles↗
PubMed1996

[Use of molecular cytogenetic techniques for establishing the origin of chromosome markers in patients with Turner phenotype].

Results of marker chromosome identification using the FISH technique are presented. The origin of markers was determined in 11 patients with mosaic karyotype 45,X/46,X,mar. Using probes specific for X and Y chromosomes, we demonstrated that in 8 patients the marker originated from the X chromosome and in 3 cases it was an abnormal Y chromosome. These 3 patients were identified as at high risk for developing gonadoblastoma and prophylactic gonadectomy was performed. Results of these studies show that the FISH technique is a very useful method in the diagnosis of sex chromosome abnormalities.

Child↗
PubMed1996

[Partial trisomy of chromosome 13--diagnosis confirmed with the FISH in situ hybridization technique].

The case of a 1.5 year old girl with clinical traits of craniofacial dysmorphy, hypotonia, polydactyly and moderate mental retardation is presented. Routine cytogenetic study revealed the presence of a large additional chromosomal fragment associated with the nucleolus organizing region on one of chromosomes 13. The banding pattern suggested the additional fragment was a part of the long arm of this chromosome. The set of clinical symptoms was only partly consistent with those characteristic for trisomy 13q2 and 3. Application of the FISH technique with a chromosome 13 specific library enabled final confirmation of the origin of the extra chromosome fragment from the long arm of chromosome 13. The presented case proves the usefulness of the FISH technique for the diagnosis of chromosomal aberrations and for adequate clinical interpretation of cytogenetic results.

Abnormalities, Multiple↗
PubMed1995

[Cytogenetic studies in clinical diagnosis --analysis of 1611 examination results].

An analysis of the frequency and type of chromosome aberrations found in 1611 cytogenetic studies has been done in relation to the clinical indications. The most frequent reason for referral was: MCM/MR syndrome (15.4% cases), suspicion of sex chromosome abnormality (13.1%), Down syndrome (11.2%) and reproductive wastage (10.6%). The incidence of abnormal karyotypes in these groups of patients was 10.1%, 24.2%, 87.9% and 9.3% per couple, respectively. The lowest percentage of chromosome aberrations was found among patients with nonspecific mental retardation (2.2%) and in the families who lost a baby with MCM Syndrome (3.3% per couple). On the whole, abnormal karyotype was found in 364 patients (22.6%). Among 62 families identified by the affected child with, structural chromosome aberration in 24 families (38.7%) the abnormality was familial in the origin.

Adult↗
PubMed1995

[Reliability of cytogenetic and clinical diagnostic studies. Results of analyzing 1621 pre- and postnatal studies].

Systematic quality assessment of cytogenetic studies is very important for maintaining high standards of diagnostic testing and adequate genetic service. Results of quality assessment for 714 pre- and 907 postnatal cytogenetic studies performed in the Genetic Department of the National Research Institute of Mother and Child are presented. The assessment included: reporting time, quality of chromosome preparations, reliability and success rate of the studies. Mean reporting time for blood samples was 20 days and for amniotic fluid 23 days. Chromosome banding quality was adequate to reasons for referral in 86.9% of blood samples and in 100% of amniotic fluids. The success rate for pre- and postnatal studies was 99.4 and 96.6%, respectively. The need to develop a quality assessment scheme for clinical cytogenetics in Poland is discussed.

Diagnostic Services↗
PubMed1995

[A study evaluating the correlation between the phenotype and genotype among 65 cystic fibrosis patients].

Among 65 CF diagnosed patients with both CFTR gene mutations known genotype-phenotype studies were performed. Correlation between pancreatic insufficiency and so called "severe mutations" was found. Respiratory tract symptoms do not seem to depend on one specific mutation as well as meconium ileus is not only limited to the group of patients with delta F508/delta F508 genotype. Some other genotype - clinical features correlation in CF patients are discussed.

Adolescent↗
PubMed1994

Frequencies of the most common mutations responsible for phenylketonuria in Poland.

We screened 91 Polish phenylketonuric (PKU) children for the presence of 18 common mutations in the phenylalanine hydroxylase (PAH) gene, and 75.7% of PAH alleles were identified. The R408W mutation accounted for 54.9% of PAH mutant alleles. In the other 20.8%, eight mutations were detected: R158Q (6.6%), IVS10 (4.9%), IVS12 (2.7%), R261Q (2.2%), G272ter (1.65%), Y414C (1.1%), R252W (1.1%) and P281L (0.54%). Correlations between genotype and clinical phenotype were described.

Alleles↗