# Genetic Variants in Patients with Premature Ovarian Insufficiency in a Mexican Cohort
## 3 Results
### Pathogenic Analysis  
Table 2 illustrates the prediction scores for the genetic variants identified from study patients with POI and healthy subjects. Aside from the deleterious association indicated by PROVEAN and VarSite for the _NRIP1_ gene, all four programs (PolyPhen-2, PROVEAN, MutationTaster, and VarSite) used to predict the impact of genetic alternations on protein function indicated only neutral or benign effects; therefore, none of the genetic substitutions reported in this study were disease-associated variants. Figure 3: Schematic illustration of amplified exons from the human _WT1_ (NM_024426.6) gene located on chromosome 11. Exons (1–10) are represented by blue boxes. Partial nucleotide sequences of the human _WT1_ gene were obtained by bidirectional Sanger sequencing from patients with POI. The human genome sequence revealed that the _WT1_ gene contains four synonymous polymorphisms. Figure 4: X-chromosome and exon representations of the human _NR0 BI_ (NM_000475.5) gene. Exons (1 and 2) were analyzed by capillary electrophoresis. Human _NR0 BI_ gene sequence variants were identified in exon 1 (blue box) from patients with POI. The presented fragment of the nucleic acid sequence of the _NR0 BI_ gene contains both the non-synonymous and synonymous variants. Figure 5: _Cont._  
Figure 5: Partial nucleotide sequence of the human _NR5A1_ (NM_004959.5) gene and a structural diagram of its location on chromosome 9. Genotypic variants in the coding/non-coding regions are located in exon 4 and intron 4 (blue boxes), respectively. Exons are indicated with blue boxes. Figure 6: _Cont._  
Figure 6: Allelic variants of the human _LHX9_ (NM_020204.3) gene located on the long arm of chromosome 1. Five exons (blue boxes) were assessed by PCR-SSCP analysis and the coding/non-coding variants were identified by DNA sequencing. The locations of the substitutions are indicated above the electropherogram. Figure 7: The _ZNF275_ (NM_001080485.4) gene variant on the long arm of the X chromosome was verified by Sanger sequencing. A homozygous variant (TGT) and heterozygous variant (TGT/TGC) were found in exon 3 (blue box). \begin{table}
\begin{tabular}{c c c c c c c c c} \hline \hline \multirow{2}{*}{**Gene**} & **Nucleotide** & \multirow{2}{*}{**Genotype**} & \multirow{2}{*}{**Reference**} & \multirow{2}{*}{**Function**} & \multirow{2}{*}{**Genotype**} & \multirow{2}{*}{**Allele Frequencies**} & \multirow{2}{*}{**Geneotype**} & \multirow{2}{*}{**Frequentcies**} & \multirow{2}{*}{**Allele Frequencies**} \\  & & & & & (POI) & & (Controls) & \\ \hline _WT1_ & c.213G\(\rightarrow\)T & G/G & rs2234582 & Synonymous & 0.09 & p = 0.135 & 0.1 & p = 0.15 \\  & & T/T & & 0.82 & q = 0.865 & 0.8 & q = 0.85 \\  & & G/T & & 0.09 & 0.1 & & \\  & c.609T\(\rightarrow\)C & C/C & This study & Synonymous & 0.91 & p = 0.955 & 0.93 & p = 0.965 \\  & & T/T & & 0.0 & q = 0.045 & 0.0 & q = 0.035 \\  & & T/C & & 0.09 & & 0.07 & \\  & c.873A\(\rightarrow\)G & G/G & This study & Synonymous & 0.91 & p = 0.955 & 0.9 & p = 0.95 \\  & & A/A & & 0.0 & q = 0.045 & 0.0 & q = 0.05 \\  & & A/G & & 0.09 & & 0.1 & \\  & c.1122G\(\rightarrow\)A & G/G & This study & Synonymous & 0.18 & p = 0.41 & 0.13 & p = 0.39 \\  & & A/A & & 0.36 & q = 0.59 & 0.35 & q = 0.61 \\  & & G/A & & 0.46 & & 0.52 & \\ _NR0B1_ & c.353C\(\rightarrow\)T & C/C & This study & Non- & 0.91 & p = 0.955 & 0.94 & p = 0.97 \\  & & T/T & & 0.0 & q = 0.045 & 0.0 & q = 0.03 \\  & & C/T & & 0.09 & & 0.06 & \\  & c.425G\(\rightarrow\)A & A/A & This study & Synonymous & 0.18 & p = 0.36 & 0.16 & p = 0.355 \\  & & G/G & & 0.46 & q = 0.64 & 0.45 & q = 0.645 \\  & & G/A & & 0.36 & & 0.39 & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: A summary of the genotype and allele frequencies for the _WT1_ (NM_024426.6), _NR0B1_ (NM_000475.5), _NR5A1_ (NM_004959.5), _LHX9_ (NM_020204.3), _ZNF275_ (NM_001080485.4), and _NRUP1_ (NM_003489.4) genes from patients with POI (n = 11) and healthy controls (n = 100) in the Mexican population.