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1

Polish Registry of Congenital Malformations ? aims and organization of the registry monitoring 300 000 births a year

100%

Latos-Bielenska A., Materna-Kiryluk A.

Journal of Applied Genetics

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2005

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vol. 46

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issue 4

341-348

EN

In 1997, the Polish Registry of Congenital Malformations (PRCM) was established, to fulfil epidemiological, prophylactic, socioeconomic and scientific functions. The PRCM is a population-based registry monitoring currently about 300 000 births a year in 13 provinces. Such a large area and population require a special organizational structure of the Registry. The PRCM Central Working Group and the computer database are located in the Department of Medical Genetics, University of Medical Sciences, Pozna?. Here the data are collected, validated, encoded according to the ICD-10, and analysed. Provincial Working Groups are responsible for supervision of data collection in the given province. The PRCM staff has grown from about 250 members in 1997 to more than 400 members today. The PRCM collects information on structural defects diagnosed before the end of the second year of life. Minor anomalies are excluded from the registry. The main source of information is a registration form filled up by the physician diagnosing the anomaly. Since 2004 also electronic reporting has been possible. On 28 September 2005 there were 54 020 entries in the database concerning 33 729 children with at least one congenital malformation and 1261 control entries concerning children without malformations. The PRCM is also an important source of identification of families at genetic risk. Education of physicians and the community in the field of genetic counselling is also an important aim of the PRCM. Since 2001, the PRCM has been a member of the Eurocat. Detailed information on PRCM organization, electronic reporting, and results are available at the PRCM website (www.rejestrwad.pl).

2

Collagens, the basic proteins of the human body

81%

Czarny-Ratajczak M., Latos-Bielenska L.-B. A., Latos-Bielenska A.

Journal of Applied Genetics

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2000

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vol. 41

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issue 4

317-330

EN

Collagens are structural elements of many tissues in the human body. The family of collagens can be divided into fibrillar and non-fibrillar collagens. The criterion of the classification is the structure of these proteins. Mutations in the genes encoding collagens cause a variety of human diseases that include osteogenesis imperfecta, some forms of osteoporosis, chondrodysplasias, some types of Ehlers-Danlos syndrome, arterial and intracranial aneurysms, epidermolysis bullosa and the renal disease known as Alport syndrome. The detection of mutations is important both scientifically and clinically. Defining the molecular defects underlying a disorder helps in the understanding of not only the properties of the mutated protein but also the function of the normal protein. Even though many mutations in the genes encoding collagens have been described, the pathogenic consequences of some of the mutations are not fully understood. The important rationale for mutation detection is the clinical use of molecular diagnostics in genetic counselling and differential diagnosis.

3

Only neutral polymorphisms found in the TIGR/myocilin gene of 45 Polish patients with primary open-angle glaucoma

81%

Krawczynski M. R., Czarny-Ratajczak M., Pecold K., Latos-Bielenska A.

Journal of Applied Genetics

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2004

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vol. 45

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issue 2

275-279

EN

The aim of the study was to identify mutations of the TIGR gene in Polish patients with primary open-angle glaucoma (POAG) and to define possible genotype-phenotype correlations. The study included 45 patients with a verified diagnosis of POAG. The PCR amplification of all three exons of the TIGR gene and screening for the sequence changes by CSGE analysis was done for every patient. The probes with identified heteroduplexes were sequenced. Altogether 315 PCR products were obtained. The CSGE analysis detected 60 possible changes of the sequence in 28 patients. 34 heteroduplexes were chosen for sequencing, including 29 unique changes and 5 changes representative of identical heteroduplexes. Direct sequencing enabled detection of only four different changes in the TIGR gene sequence. Three of them: 5?UTR ?83GA (in 14 patients), +227 exon 1 GA, Arg76Lys (in 14 patients) and +311 exon 3 TC, Tyr347Tyr (in 4 patients) have already been described in the literature as neutral polymorphisms of the gene. Only one change in the promoter, 5?UTR ?126TC (in 2 patients), has not been described in the literature to date. However, this change does not alter directly the sequence of amino acids in myocilin, so it is difficult to conclude on its pathogenetic role. Thus our study showed only neutral polymorphisms of the TIGR gene. This suggests that the patients probably have mutations in other genes, so other loci that predispose to POAG must be analyzed.

4

A familial X/Y translocation: cytogenetic and molecular study

71%

Kusz K., Wojda A., Wisniewska M., Latos-Bielenska A., Jaruzelska J.

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issue 2

237-240

EN

In this study we describe a 3-generation family carrying a (X;Y)(p22.3;q11.2) translocation in seven individuals of both sexes. Molecular analysis of the aberrant (X;Y)(p22.3;q11.2) chromosome was performed by FISH using X and Y-specific painting probes and also PCR amplification of the Y-specific sequences. Using these approaches it was demonstrated that the translocation resulted in a deletion of both X and Y pseudoautosomal regions. Moreover, using RBG banding it was shown that in all females the X-derivative chromosome was inactive in over 90% of mitoses. From the preliminary results obtained in this study we assumed that in this particular family the observed phenotype of the patients was caused by a deletion of the cluster of pseudoaotosomal genes responsible for the stature. More proximal loci, like STS or MRX49, were probably not deleted, since neither ichtyosis nor mental retardation was observed in this family.

5

A new case of DOOR syndrome

61%

Wisniewska M., Siwinska Z., Felczak M., Wielkoszynski T., Krawczynski M., Latos-Bielenska A.

Journal of Applied Genetics

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2008

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vol. 49

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issue 1

101-103

EN

We present the case of a 9-year-old boy with DOOR syndrome recognized in the first year of his life because of a delayed development of speech. The diagnosis was based on characteristic abnormalities, including congenital deafness, nail and bone abnormalities, and mild mental retardation

6

Subtle familial translocation t(11;22)(q24.2;q13.33) resulting in Jacobsen syndrome and distal trisomy 22q13.3: further details of genotype?phenotype maps

52%

Jamsheer A., Smyk M., Wierzba J., Kolowska J., Wozniak A., Skolozdrzy J., Fischer M., Latos-Bielenska A.

Journal of Applied Genetics

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2008

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vol. 49

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issue 4

397-405

EN

We report on 3 kindred patients with terminal 11q monosomy and distal 22q trisomy involving the SHANK3 gene, resulting from a subtle familial translocation t(11;22)(q24.2;q13.33). The patients presented with the characteristic symptoms of Jacobsen syndrome (JBS), including: mental retardation, short stature, and craniofacial dysmorphism in all 3 cases; cardiac defects in 2 cases; and thrombocytopenia, brain abnormality, eye coloboma, recurrent infections, cryptorchidism and toe anomalies in single cases. The oldest patient also had Hashimoto disease and diabetes mellitus type 2. So far, these 2 conditions have not been reported in adult patients with JBS. Features typical for distal 22q trisomy in our patients include muscular hypotonia and prenatal failure to thrive, seen in 2 and 1 cases, respectively. We also present a family member with 11q24.2-qter trisomy and 22q13.33-qter monosomy, whose clinical phenotype is partially overlapping with several dysmorphic features of JBS. In addition, multiple pregnancy losses and infantile deaths occurred in this family, suggesting that these chromosomal imbalances may produce a lethal phenotype. FISH with a panel of BAC probes determined the accurate sizes of the deletion 11q (9.9 Mb) and trisomy 22q (0.8 Mb). To date, only 5 cases of submicroscopic 22q13.3-qter trisomy have been reported. A detailed clinical description of our patients, along with a precise cytogenetic designation of chromosomal breakpoints, allow further refinement of genotype-phenotype correlation for distal imbalances in 11q and 22q.

7

Molecular genetic diagnosis of the 1.5 Mb deletion causing hereditary neuropathy with liability to pressure palsies (HNPP) in a Polish family

52%

Kochanski A. M., Lofgren A., Timmerman V., Jedrzejewska H., Fidzinska A., Latos-Bielenska A., van_Browckhoven C., Hausmanowa-Petrusewic

Journal of Applied Genetics

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1999

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vol. 40

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issue 3

249-255

EN

A molecular genetic analysis was performed in one Polish family with hereditary neuropathy with liability to pressure palsies (HNPP), using two distinct molecular genetic methods, i.e. RFLP and STR analysis. This permitted to reveal the presence of a 17p11.2 HNPP deletion both in the proband and in her mother. The molecular analysis in the proband was supplemented with nerve conduction rate tests and sural nerve biopsy. We conclude that the relatively low prevalence of HNPP in Poland is caused most probably by lack of access to molecular genetic testing. In the future HNPP molecular testing should be offered to all patients in Poland.

8

A novel GJA1 missense mutation in a Polish child with oculodentodigital dysplasia

52%

Jamsheer A., Wisniewska M., Szpak A., Bugaj G., Krawczynski M. R., Budny B., Wawrocka A., Latos-Bielenska A.

Journal of Applied Genetics

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2009

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vol. 50

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issue 3

297-299

EN

Oculodentodigital dysplasia (ODDD) (OMIM #164200) is a rare congenital, autosomal dominant disorder comprising craniofacial, ocular, dental, and digital anomalies. The syndrome is caused by GJA1 mutations. The clinical phenotype of ODDD involves a characteristic dysmorphic facies, ocular findings (microphthalmia, microcornea, glaucoma), syndactyly type III of the hands, phalangeal abnormalities, diffuse skeletal dysplasia, enamel dysplasia, and hypotrichosis. In a Polish child with the clinical symptoms typical of ODDD, we demonstrated a novel missense mutation c.C31A resulting in p.L11F substitution. Our report provides evidence on the importance of this highly conserved amino acid residue for the proper functioning of GJA1 protein.

9

A new sporadic case of early-onset Loeys-Dietz syndrome due to the recurrent mutation p.R528C in the TGFBR2 gene substantiates interindividual clinical variability

52%

Jamsheer A., Henggeler C., Wierzba J., Loeys B., De_ P. A., Stheneur C., Badziag N., Matuszewska K., Matyas G., Latos-Bielenska A.

Journal of Applied Genetics

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2009

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vol. 50

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issue 4

405-410

EN

We report on a 2-year-old Polish girl with typical manifestations of Loeys-Dietz syndrome (LDS), a rare genetic condition belonging to the group of Marfan-related disorders. The characteristic LDS symptoms observed in the girl included craniofacial dysmorphism (craniosynostosis, cleft palate, hypertelorism), arachnodactyly, camptodactyly, scoliosis, joint laxity, talipes equinovarus, translucent and hyperelastic skin, and umbilical hernia. Mild dilatation of the ascending aorta and tortuous course of the left internal carotid artery were recognized during her second year of life. Molecular genetic testing revealed a heterozygous missense mutation (c.1582C>T, p.R528C) in the transforming growth factor beta receptor II gene (TGFBR2). This mutation has been previously associated with LDS in 5 unrelated cases, and was never reported in patients with other Marfan-related disorders. Comparison of the phenotypes of our patient and these 5 individuals with c.1582C>T showed that only the hallmark triad of the syndrome ? consisting of hypertelorism, aortic root dilatation/aneurysm, and cleft palate or bifid uvula ? was present in all 6 cases. Interestingly, none of the 5 individuals who underwent psychological evaluation showed developmental delay. The pattern of all other LDS features showed interindividual variability. Our data support the recently reported observation that symptoms of LDS can develop at a very young age, making early diagnosis and management essential for these patients. This is the first report on a Polish infant with typical LDS symptoms caused by a TGFBR2 mutation.

Refine search results

Polish Registry of Congenital Malformations ? aims and organization of the registry monitoring 300 000 births a year

Collagens, the basic proteins of the human body

Only neutral polymorphisms found in the TIGR/myocilin gene of 45 Polish patients with primary open-angle glaucoma

A familial X/Y translocation: cytogenetic and molecular study

A new case of DOOR syndrome

Subtle familial translocation t(11;22)(q24.2;q13.33) resulting in Jacobsen syndrome and distal trisomy 22q13.3: further details of genotype?phenotype maps

Molecular genetic diagnosis of the 1.5 Mb deletion causing hereditary neuropathy with liability to pressure palsies (HNPP) in a Polish family

A novel GJA1 missense mutation in a Polish child with oculodentodigital dysplasia

A new sporadic case of early-onset Loeys-Dietz syndrome due to the recurrent mutation p.R528C in the TGFBR2 gene substantiates interindividual clinical variability