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Article Detail
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Evaluation of pathogenic correlation in Iraqi patients with Wilson disease on different treatment protocols
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| Author:
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FADWA GHASSAN HAMEED, ASS.PROF.DR.INAMSAMEH, ASSPROFDRMOHAMMED MAHMOOD MOHAMMED
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| Abstract:
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Background: Wilson disease (WD) is an Autosomal-Recessive disorder due to mutations of ATP7B gene on
chromosome13q14.3. Inadequate protein function leads to low ceruloplasmin blood levels and copper
accumulation in liver, basal gangliaand chornea. Main clinical manifestations are hypertransaminasemia, tremors,
dysarthria, dystonia and psychiatric symptoms. The phenotypic variability in WD is considerable and its onset
can be heterogeneous: the most common type in childhood is the hepatic involvement, followed by the
neurological one or others.
Patients and methods: A total of 42 Iraqi patients diagnosed with Wilson disease
(20 males and 22 female) with age range between 10 – 20 years, who attended the Rare Disease clinic of the
Al-Imaamin AL-Kadhmian medical city Hospital –Baghdad/Iraq ,were diagnosed according to LEIPZIG score
system and genetic test were assessed to these patients by using (Sanger-Sequencing Method).
Results:Six single nucleotide polymorphisims (SNPs.) have been identified as
follows:SNP.NO.1(rs1384965287), SNP.NO.2(rs116947713), SNP.NO.3 (rs751202110),
SNP.NO.4(rs137853284), SNP.NO.5(rs751798708)and SNP.NO.6(rs1010500703). Three ATP7B gene
mutations were identified: (p.Arginine 778 Tryptophan),(p.Tyrosin 715- stop codon)and(p.Arginin778
Tryptophan). Genotype frequency shows a highly significant at p value(= 0.01)for SNPs. No.(3,4,5 and 6).Allele
frequency in SNP no.6 (C:T) , shows a highly significant at p value(= 0.01).Mean while the Odd ratio(it is
the ratio of the odds of disease in the exposed group compared with the non-exposed) was very high in SNP.
no.6 (20.72), SNP.no.5(9.497),SNP.nO.3(4.765), While for SNP.no.2 and 4 was the same (2.58).By using sanger
sequencing method, Four novel mutations were detected for the 42 Wilson’s disease patients as follows:
rs4943044 AA (Intron-non coded)with (52.3%) as a benign mutation ,rs137853284 CC (p.Arginine 778
Tryptophan ) with (92.8%)and rs751202110 CC (p.Tyrosin 715- stop codon) with (90.4%) as a pathogenic
mutations meanwhile the rs751798708 TT (p.Arginin778 Tryptophan) with (85.7%) is considered as likely
pathogenic. There was no significant difference (P=0.13) between the three mutations (pathogenic, likely
pathogenic and benign) among the study groups. The percentage of pathogenic mutation was 90 % in DPenicillamin group, 77.8% in Trinetin group and 56.5% in Zinc Acetate group. Likely Pathogenic mutation
percentage was 10 % in D-Penicillamin, 22.2% in Trinetin and 43.5% in Zinc Acetate groups while,the
percentage of Benign Mutation was 90% in D- penicillamin,67% in Trinetin and 83% in Zinc Acetate groups.
Conclusion: The intervention of modifier genes regulating copper metabolism in the presence of mutations
ATP7B,as in WD, could be considered. Heterogeneous clinical presentations, probably, could not depend only
on ATP7B degree of functional alterations or genetic mutation.
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| Keyword:
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Wilson disease, Benign, Pathogenic, LikelyPathogenic, Single nucleotide polymorphisims (SNPs.).
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| EOI:
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| DOI:
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https://doi.org/10.31838/ijpr/2021.13.02.169
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| Download:
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