Finnish-type aspartylglucosaminuria detected by oligonucleotide ligation assay

1995 ◽  
Vol 41 (1) ◽  
pp. 59-61 ◽  
Author(s):  
C M Delahunty ◽  
W Ankener ◽  
S Brainerd ◽  
D A Nickerson ◽  
I T Mononen
Keyword(s):  
Storage Disease ◽  
Large Population ◽  
Lysosomal Storage ◽  
Finnish Population ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Single Nucleotide Change ◽  
Normal Carrier ◽  
Oligonucleotide Ligation Assay ◽  
Polymerase Chain

Abstract Aspartylglycosaminuria (AGU) is a recessively inherited lysosomal storage disease that occurs with much higher frequency in Finland than elsewhere. AGU is caused by a deficiency in glycosylasparaginase (GA), which results in the accumulation of glycoasparagines in lysosomes. In the Finnish population, a single nucleotide change in the gene encoding GA is responsible for the disease. We have used the oligonucleotide ligation assay (OLA) to detect the mutation in polymerase chain reaction (PCR)-amplified DNA samples from normal, carrier, and affected individuals. Screening for AGU among 415 random Finnish DNA samples with PCR/OLA revealed five carriers of the mutant allele and demonstrated the potential of the method for use in carrier screening. PCR/OLA provides a rapid, reliable, nonisotopic method to detect the mutation responsible for AGU that can readily be applied to large population screening.

scholarly journals Prevalence of congenital non syndromic hearing loss among offspring of consanguineous marriage: a pilot study

2020 ◽  
Vol 6 (5) ◽  
pp. 874
Author(s):  
Gangadhar K. S. ◽  
Geetha Bhaktha ◽  
Manjula B. ◽  
Nageshwari P.
Keyword(s):  
Hearing Loss ◽  
Consanguineous Marriage ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Junction Protein ◽  
Study Population ◽  
Syndromic Hearing Loss ◽  
Gap Junction Protein ◽  
Polymerase Chain ◽  
Recessive Defect

<p class="abstract"><strong>Background:</strong> Mutations in the gene encoding the gap-junction protein connexin-26, is understood to be the most important cause of non-syndromic hearing loss (NSHL). An attempt to identify the single nucleotide polymorphism (SNP) for W24X mutation was done.  Consanguineous marriage was seen among the NSHL subjects.</p><p class="abstract"><strong>Methods:</strong> SNP was identified using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR).  Forty-five subjects were screened for congenital hearing loss. Twenty subjects matched the inclusion criteria and were included in the study.</p><p class="abstract"><strong>Results:</strong> 5 out of 20 subjects were found to have mutation i.e., 25%. Though consanguinity is known to cause autosomal recessive defect, the same could not be depicted in this study.</p><p class="abstract"><strong>Conclusions:</strong> 25% of the study population had a mutation in their gene and the rest though had consanguineous marriage had not been affected genotypically.</p>

scholarly journals Molecular basis for the human erythrocyte glycophorin specifying the Miltenberger class I (MiI) phenotype

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 257-263 ◽  
Author(s):  
CH Huang ◽  
P Spruell ◽  
JJ Moulds ◽  
OO Blumenfeld
Keyword(s):  
Molecular Basis ◽  
Consensus Sequence ◽  
Direct Repeat ◽  
Single Copy ◽  
Class I ◽  
Blood Group System ◽  
White Family ◽  
Single Nucleotide ◽  
Single Nucleotide Change ◽  
Polymerase Chain

Abstract Human glycophorin Mil (HGpMil) is a structural variant of the MNSs blood group system that specifies the Miltenberger class I phenotype. We report here the molecular basis of the HGpMil gene identified in a white family in which the first homozygote was encountered. Immunoblotting analysis showed the expression of HGpMil and HGpB but the absence of HGpA on the homozygous Mil erythrocytes. Southern blot analysis detected no gross alterations in gene structure or band intensity. Genomic sequences encompassing exons II and III of the HGpMil gene were amplified by single-copy polymerase chain reaction. Restriction digestion and direct DNA sequence analysis showed that HGpMil gene is derived from an alpha N allele of HGpA and differs from the latter in the third exon by a single nucleotide change. In HGpMil, the presence of a deoxythymidine at the second position of codon 28 (ATG) not only resulted in a methionine substitution but also altered the consensus sequence for N-glycosylation from Asn-Asp-Thr to Asn-Asp- Met. These data are consistent with the occurrence of Mil on the red blood cell membrane as a variant deficient in the asparagine-linked carbohydrate unit. Significantly, this particular point mutation lies in between the two half-sites of a direct repeat that has been implicated to facilitate the recombination events leading to several other glycophorin genes of the Miltenberger series. Based on this relatedness, we propose an untemplated nucleotide replacement resulting from a gene conversion event as the molecular basis for the origin of HGpMil gene.

Glucocerebrosidase, a new player changing the old rules in Lewy body diseases

2013 ◽  
Vol 394 (7) ◽  
pp. 807-818 ◽  
Author(s):  
Na-Young Yang ◽  
Yu-Na Lee ◽  
He-Jin Lee ◽  
Yoon Suk Kim ◽  
Seung-Jae Lee
Keyword(s):  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Storage Disease ◽  
Lewy Bodies ◽  
Mechanisms Of Action ◽  
Lysosomal Storage ◽  
Gene Encoding ◽  
Glycolipid Metabolism ◽  
Lewy Body Diseases

AbstractMutations in the gene encoding glucocerebrosidase (GBA1) cause Gaucher disease (GD), a lysosomal storage disease with recessive inheritance. Glucocerebrosidase (GCase) is a lysosomal lipid hydrolase that digests glycolipid substrates, such as glucosylceramide and glucosylsphingosine.GBA1mutations have been implicated in Lewy body diseases (LBDs), such as Parkinson’s disease and dementia with Lewy bodies. Parkinsonism occurs more frequently in certain types of GD, andGBA1mutation carriers are more likely to have LBDs than non-carriers. Furthermore, GCase is often found in Lewy bodies, which are composed of α-synuclein fibrils as well as a variety of proteins and vesicles. In this review, we discuss potential mechanisms of action ofGBA1mutations in LBDs with particular emphasis on α-synuclein aggregation by reviewing the current literature on the role of GCase in lysosomal functions and glycolipid metabolism.

Molecular detection and analysis of a novel metalloprotease gene of entomopathogenic Serratia marcescens strains in infected Galleria mellonella

2014 ◽  
Vol 60 (4) ◽  
pp. 203-209 ◽  
Author(s):  
J.T. Tambong ◽  
R. Xu ◽  
A. Sadiku ◽  
Q. Chen ◽  
A. Badiss ◽  
...  
Keyword(s):  
Serratia Marcescens ◽  
Aspartic Acid ◽  
Galleria Mellonella ◽  
Residue Analysis ◽  
Protein Detection ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Aspartic Acid Residue ◽  
Polymerase Chain

Serratia marcescens strains isolated from entomopathogenic nematodes (Rhabditis sp.) were examined for their pathogenicity and establishment in wax moth (Galleria mellonella) larvae. All the Serratia strains were potently pathogenic to G. mellonella larvae, leading to death within 48 h. The strains were shown to possess a metalloprotease gene encoding for a novel serralysin-like protein. Rapid establishment of the bacteria in infected larvae was confirmed by specific polymerase chain reaction (PCR) detection of a DNA fragment encoding for this protein. Detection of the viable Serratia strains in infected larvae was validated using the SYBR Green reverse transcriptase real-time PCR assay targeting the metalloprotease gene. Nucleotide sequences of the metalloprotease gene obtained in our study showed 72 single nucleotide polymorphisms (SNP) and 3 insertions compared with the metalloprotease gene of S. marcescens E-15. The metalloprotease gene had 60 synonymous and 8 nonsynonymous substitutions relative to the closest GenBank entry, S. marcescens E-15. A comparison of the amino acid composition of the new serralysin-like protein with that of the serralysin protein of S. marcescens E-15 revealed differences at 11 positions and a new aspartic acid residue. Analysis of the effect of protein variation suggests that a new aspartic acid residue resulting from nonsynonymous nucleotide mutations in the protein structure could have the most significant effect on its biological function. The new metalloprotease gene and (or) its product could have applications in plant agricultural biotechnology.

scholarly journals Association of eNOS Gene Polymorphisms T-786C and G894T With Blood Pressure Variability in Man

2011 ◽  
pp. 193-197 ◽  
Author(s):  
M. JÍRA ◽  
E. ZÁVODNÁ ◽  
N. HONZÍKOVÁ ◽  
Z. NOVÁKOVÁ ◽  
A. VAŠKŮ ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Variability ◽  
Spectral Power ◽  
Restriction Analysis ◽  
Enos Gene ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Polymerase Chain ◽  
Frequent Allele

The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) T-786C and G894T in the gene encoding eNOS with blood pressure variability (BPV) in man. Blood pressure was recorded beat-to-beat at rest three times in periods of one week (5 min, Finapres, breathing at 0.33 Hz) in 152 subjects (19-24 years). Systolic (SBPV0.1r/SBPV0.1a) and diastolic (DBPV0.1r/DBPV0.1a) blood pressure variabilities in relative (r.u.) and absolute (mmHg2/Hz) units were determined by the spectral method as spectral power at the frequency of 0.1 Hz. Genotypes of both polymorphisms were detected using polymerase chain reaction and restriction analysis using enzymes Msp I and Ban II. Significant differences were observed in BPV among genotypes of T-786C SNP (p<0.05; Kruskal-Wallis), and among haplotypes of both SNPs (p<0.05; Kruskal-Wallis) as well. In T-786C SNP, carriers of less frequent allele (CC homozygotes and TC heterozygotes) showed significantly greater SBPV0.1r and SBPV0.1a compared to TT homozygotes (Mann-Whitney; p<0.05). The G894T variant showed no significant differences, but, both SNPs were in linkage disequilibrium (D’=0.37; p<0.01). Carriers of haplotype CT/CT (CC homozygotes of -786C/T and TT homozygotes of G894T) displayed significantly greater SBPV0.1r, SBPV0.1a and DBPV0.1a compared to carriers of other haplotype combinations (Kruskal-Wallis; p=0.015, p=0.048, and p=0.026, respectively). In conclusion, the haplotype formed by less frequent alleles of both eNOS variants was associated with increased systolic and diastolic BPV in this study.

scholarly journals Molecular basis for the human erythrocyte glycophorin specifying the Miltenberger class I (MiI) phenotype

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 257-263
Author(s):  
CH Huang ◽  
P Spruell ◽  
JJ Moulds ◽  
OO Blumenfeld
Keyword(s):  
Molecular Basis ◽  
Consensus Sequence ◽  
Direct Repeat ◽  
Single Copy ◽  
Class I ◽  
Blood Group System ◽  
White Family ◽  
Single Nucleotide ◽  
Single Nucleotide Change ◽  
Polymerase Chain

Human glycophorin Mil (HGpMil) is a structural variant of the MNSs blood group system that specifies the Miltenberger class I phenotype. We report here the molecular basis of the HGpMil gene identified in a white family in which the first homozygote was encountered. Immunoblotting analysis showed the expression of HGpMil and HGpB but the absence of HGpA on the homozygous Mil erythrocytes. Southern blot analysis detected no gross alterations in gene structure or band intensity. Genomic sequences encompassing exons II and III of the HGpMil gene were amplified by single-copy polymerase chain reaction. Restriction digestion and direct DNA sequence analysis showed that HGpMil gene is derived from an alpha N allele of HGpA and differs from the latter in the third exon by a single nucleotide change. In HGpMil, the presence of a deoxythymidine at the second position of codon 28 (ATG) not only resulted in a methionine substitution but also altered the consensus sequence for N-glycosylation from Asn-Asp-Thr to Asn-Asp- Met. These data are consistent with the occurrence of Mil on the red blood cell membrane as a variant deficient in the asparagine-linked carbohydrate unit. Significantly, this particular point mutation lies in between the two half-sites of a direct repeat that has been implicated to facilitate the recombination events leading to several other glycophorin genes of the Miltenberger series. Based on this relatedness, we propose an untemplated nucleotide replacement resulting from a gene conversion event as the molecular basis for the origin of HGpMil gene.

scholarly journals Molecular diagnosis of medium-chain acyl-CoA dehydrogenase deficiency by oligonucleotide ligation assay

1998 ◽  
Vol 44 (1) ◽  
pp. 68-71 ◽  
Author(s):  
Eeva-Liisa Romppanen ◽  
Tarja Mononen ◽  
Ilkka Mononen
Keyword(s):  
Sequence Variation ◽  
Dehydrogenase Deficiency ◽  
Confidence Limits ◽  
Mcad Deficiency ◽  
Single Nucleotide ◽  
Medium Chain ◽  
Single Nucleotide Change ◽  
Allelic Sequence ◽  
Chain Acyl ◽  
Oligonucleotide Ligation Assay

Abstract Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a recessively inherited defect in the mitochondrial β-oxidation of fatty acids. A single nucleotide change, the A985→G transition, in the MCAD gene accounts for ∼90% of all the disease-causing mutations in the patients. We have used PCR to amplify a segment of the human MCAD gene and typed the allelic sequence variation at base 985 by a colorimetric oligonucleotide ligation assay (OLA). PCR/OLA provides a technique that permits differentiation of the homozygotes, heterozygotes, and normals for the A985→G allele in the MCAD gene. Genotyping of 1908 random Finnish DNA samples by OLA identified 10 carriers of the mutant allele, but no homozygotes were found. The calculated carrier frequency for the A985→G mutation was 1:191 (95% confidence limits, 1:118–1:501), and the calculated frequency for the A985→G homozygotes was 1:147 000 (95% confidence limits, 1:56 000–1:1 004 000).

Is there a role for scintigraphic imaging of bone manifestations in Gaucher disease?

2008 ◽  
Vol 47 (06) ◽  
pp. 239-247 ◽  
Author(s):  
S. Kohlfürst ◽  
H. J. Gallowitsch ◽  
E. Kresnik ◽  
P. Lind ◽  
A. B. Mehta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lysosomal Storage Disease ◽  
Gaucher Disease ◽  
Storage Disease ◽  
Lysosomal Storage ◽  
Scintigraphic Imaging ◽  
Imaging Methods ◽  
X Ray ◽  
Deficient Activity

SummaryGaucher disease is the most prevalent inherited, lysosomal storage disease and is caused by deficient activity of the enzyme β-glucocerebrosidase. Bone and bone marrow alterations are frequent in the most prevalent non-neuronopathic form of Gaucher disease. Imaging of bone manifestations in Gaucher disease is performed by a variety of imaging methods, conventional X-ray and MRI as the most frequently and most important ones. However, different modalities of scintigraphic imaging have also been used. This article gives an overview on scintigraphic imaging with respect to bone manifestations in Gaucher disease discussing the advantages and limitations of scintigraphic imaging in comparison to other imaging methods.

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