Pathogenicity prediction of PTS: c.۷۰C>G (p.H۲۴D) variant, identified recently in an Iranian PTPS patient

  • سال انتشار: 1400
  • محل انتشار: کنفرانس بین المللی ژنتیک و ژنومیکس انسانی
  • کد COI اختصاصی: CHGGE01_370
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 57
دانلود فایل این مقاله

نویسندگان

Keivan Moradi

Department of Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

Sahand Khamooshian

Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

چکیده

Backgrounds: BH۴ is known as an essential cofactor for phenylalanine hydroxylase enzyme(PAH). Genetic mutations occurred in the genes related to this cofactor, including PTS, may leadto hyper-phenylalaninemia (HPA). In the present study, we used multiple in silico tools topredict the pathogenicity of PTS: c.۷۰C> G (p.H۲۴D), a variant recently identified in an Iranianpatient with PTPS deficiency. Subsequently, it was classified based on ACMG-AMP guidelines.Materials and Methods: To predict the nature of deleterious or neutrality of PTS: c.۷۰C> G(p.H۲۴D), a total of ۱۰ in silico tools including: CADD, Mutation Taster, Polyphen-۲, I-Mutantdisease, PROVEAN, SIFT, SNPs&GO, FATHMM-XF, PhD-SNPg, and PANTHER PSEP wereused. To assign the ACMG-AMP criteria related to this variant, a literature search wasperformed in multiple online databases.Results: All predictive tools used in this study showed deleterious effects for PTS: c.۷۰C> G(p.H۲۴D) variant. Therefore, PP۳ criterion was applied for this variant. Two other criteriaincluding PM۲ and PP۴ were also assigned. Based on these observations, PTS: c.۷۰C> G(p.H۲۴D) was classified as a VUS variant.Conclusion: PTS: c.۷۰C> G (p.H۲۴D) has only recently been identified in an Iranian PTPSpatient in homozygous form and has not been reported in public mutational databases. Therefore,its classification as a VUS variant was not unexpected. Considering that so far only two studies,with a total sample size of ۶۰ cases, have been performed in the field of identifying PTS-genemutations among Iranian PTPS patients, it is possible that this variant will be seen again in Iranin the future.

کلیدواژه ها

BH۴, PAH, hyper-phenylalaninemia (HPA)

اطلاعات بیشتر در مورد COI

COI مخفف عبارت CIVILICA Object Identifier به معنی شناسه سیویلیکا برای اسناد است. COI کدی است که مطابق محل انتشار، به مقالات کنفرانسها و ژورنالهای داخل کشور به هنگام نمایه سازی بر روی پایگاه استنادی سیویلیکا اختصاص می یابد.

کد COI به مفهوم کد ملی اسناد نمایه شده در سیویلیکا است و کدی یکتا و ثابت است و به همین دلیل همواره قابلیت استناد و پیگیری دارد.