Results found: 3

Number of results on page

Search results

Sort By:

Limit search:

Different mutations in Polish patients with HPRT deficiency - the Lesch-Nyhan and Kelley-Seegmiller syndromes

100%

Popowska E., Sulek A., Kubalska J., Jezewska M., Trembacz H., Goryluk-Kozakiewicz B., Krajewska-Walasek M.

Journal of Applied Genetics

1998

vol. 39

issue 1

103-111

Five families with the Lesch-Nyhan syndrome (LNS) and two families with the Kelley-Seegmiller syndrome (KSS) were studied. Seven different mutations were identified. Two transitions, C526?T (Pro176Ser) and G481?A (Ala161Thr), in patients with a milder form of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency were detected. In patients with the Lesch-Nyhan syndrome two transitions, G569?A (Gly190Glu) and C508?T (Arg170Ter), two transversions, C222?A (Phe74Leu) and C482?A (Ala161Glu), and a deletion of seven nucleotides (from A394 to G400) were observed. All except two of the identified mutations are novel. The C222?A substitution in exon III is located within one of the clusters of hot spots of the HPRT gene and has been previously described in four unrelated patients. The other recurrent mutation C508?T in exon VII has been reported in eight families.

Clinical course of homozygous familial hypercholesterolemia during childhood: report on 4 unrelated patients with homozygous or compound heterozygous mutationsin the LDLR gene

84%

Kubalska J., Chmara M., Limon J., Wierzbicka A., Prokurat S., Szaplyko J., Kowalik A., Mierzewska H., efesche J. C., Pronicka E.

Journal of Applied Genetics

2008

vol. 49

issue 1

109-113

Natural history of the disease in 4 unrelated Polish children with homozygous familial hypercholesterolemia (FH) is described. Their phenotypic homozygosity was established by identification of known LDLR gene mutations on both alleles, respectively: p.G592E & p.G592E in Patient 1; p.G592E & p.C667Y in Patient 2; p.S177L & p.R350X in Patient 3; and p.G592E & deletion in the promoter region, exons 1 and 2 in Patient 4. Heterozygosity of the mutations was revealed in all patients' mothers and fathers (obligatory heterozygotes) and in 1 out of 4 siblings studied. FH was diagnosed at the age of 4 months to 9 years by cholesterol screening among family members of patients with early cardiovascular disease episodes. At the time of FH detection, the children were asymptomatic. Only in 2, some skin eruptions were found. Antihyperlipidemic therapy was started, including a lipid-lowering diet, cholestyramine, and HMG-CoA inhibitors if necessary. No cardiovascular symptoms appeared during the observation up to the age of 18, 20, 19, and 17 years, respectively. An increase in external carotid artery diameter was found in a patient at the age of 9 years, and LDL-apheresis was introduced in his therapy. We conclude that the analysis of LDLR gene mutations in the studied FH children made it possible to identify 4 presymptomatic FH homozygotes and to introduce early appropriate treatment. Multicenter analysis of such persons would finally determine if the early lipid-lowering procedures can significantly reduce the risk of premature cardiovascular disease in homozygous FH.

Molecular characterization of Polish patients with familial hypercholesterolemia: novel and recurrent LDLR mutations

68%

Chmara M., Wasag B., Zuk M., Kubalska J., Wegrzyn A., Bednarska-Makaruk M., Pronicka E., Wehr H., Defesche J. C., Rynkiewicz A., Limon J.

vol. 51

issue 1

95-106

Autosomal dominant hypercholesterolemia (ADH) is caused by mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9). In this study, a molecular analysis of LDLR and APOB was performed in a group of 378 unrelated ADH patients, to explore the mutation spectrum that causes hypercholesterolemia in Poland. All patients were clinically diagnosed with ADH according to a uniform protocol and internationally accepted WHO criteria. Mutational analysis included all exons, exon-intron boundaries and the promoter sequence of the LDLR, and a fragment of exon 26 of APOB. Additionally, the MLPA technique was applied to detect rearrangements within LDLR. In total, 100 sequence variations were identified in 234 (62%) patients. Within LDLR, 40 novel and 59 previously described sequence variations were detected. Of the 99 LDLR sequence variations, 71 may be pathogenic mutations. The most frequent LDLR alteration was a point mutation p.G592E detected in 38 (10%) patients, followed by duplication of exons 4?8 found in 16 individuals (4.2%). Twenty-five cases (6.6%) demonstrated the p.R3527Q mutation of APOB. Our findings imply that major rearrangements of the LDLR gene as well as 2 point mutations (p.G592E in LDLR and p.R3527Q in APOB) are frequent causes of ADH in Poland. However, the heterogeneity of LDLR mutations detected in the studied group confirms the requirement for complex molecular studies of Polish ADH patients.

Refine search results

3 Journal of Applied Genetics

1 2010

1 2008

1 1998

3 Kubalska J.

2 Chmara M.

2 Limon J.

2 Pronicka E.

1 Bednarska-Makaruk M.

1 Defesche J. C.

1 Goryluk-Kozakiewicz B.

1 Jezewska M.

1 Kowalik A.

1 Krajewska-Walasek M.

1 Mierzewska H.

1 Popowska E.

1 Prokurat S.

1 Rynkiewicz A.

1 Sulek A.

1 Szaplyko J.

1 Trembacz H.

1 Wasag B.

1 Wegrzyn A.

1 Wehr H.

1 Wierzbicka A.

1 Zuk M.

1 efesche J. C.

Search results

Different mutations in Polish patients with HPRT deficiency - the Lesch-Nyhan and Kelley-Seegmiller syndromes

Clinical course of homozygous familial hypercholesterolemia during childhood: report on 4 unrelated patients with homozygous or compound heterozygous mutationsin the LDLR gene

Molecular characterization of Polish patients with familial hypercholesterolemia: novel and recurrent LDLR mutations