Are Variants of NOBOX’s Exon ۴ Associated withPremature Ovarian Insufficiency?

Background: Premature ovarian insufficiency (POI) is a diseasethat disrupts the normal function of the ovaries in womenbefore the age of ۴۰ and Several factors have effects on its occurrence.The newborn ovary homeobox gene (NOBOX) is anoocyte-specific gene that plays an important role in folliculogenesisand oocyte development. NOBOX is one of the genesrelated to POI. The aim of this s tudy was to inves tigate the associationbetween NOBOX and POI in Iranian patients.Materials and Methods: Through an in silico preliminaryapproach, the reported NOBOX single nucleotide variants(SNVs) in ClinVar as a valid database were inves tigated forclassification of the genetic variations considering their clinicalimportance. Next, the ClinVar SNVs was checked in Iranome,an exome sequencing-based database for frequency ofSNVs in Iranian general population; Then, the SNVs that hadbeen reported in both ClinVar and Iranome excluding benignand likely benign SNVs were selected. The wet lab s tudy wasperformed on ۱۰۰ Iranian women with POI. The inclusion andexclusion criteria were based on the ESHRE ۲۰۱۵ guideline.The polymerase chain reaction (PCR) and sanger sequencingwere performed on blood DNA. Sanger sequencing analysiswas conducted by finch tv.Results: rs۱۸۷۲۷۳۷۰۹, which is located in exon ۴ of NOBOX,was targeted because it has been previously reported in the Iraniangeneral population according to the Iranome database andits uncertain clinical significance in POI. A ۷۰۹ base pairs PCRproduct was used for Sanger sequencing. NOBOX’s exon ۴ inaddition to some of its ups tream and downs tream intronic baseswere inves tigated. The rs۱۸۷۲۷۳۷۰۹ was normal in our patientsand no other variants were found.Conclusion: Based on the Iranome we expected to findrs۱۸۷۲۷۳۷۰۹ in the s tudies patients, however no one carriedthis variant. Although this variant does not seem to be frequentin Iranian POI patients, further inves tigation with larger samplesize could be helpful for prioritization of the NOBOX variantstes ting in Iranian patients with POI.

کلیدواژه ها:

NOBOX ، Premature Ovarian Insufficiency ، SangarSequencing