Determination of inheritance frequency and heredity characteristics in accommodative and infantile esotropia cases and performing sequence analysis of myosin 13 heavy chain gene

This study aims to investigate the frequency of strabismus in the familiesof infantile ET, partial accomodative ET and accomodative ET cases and the possible genetic pattern and the role of a probable mutation in MYH 13 gene over the pathogenesis of various strabismus types in families with a high number of affected individualsin different generations. For this purpose, the family members of monitored or newly-diagnosed 139 accomodative ET, 55 partial accomodative ET and 21 congenital ET patients were included in the study. As a result of a compherensive family survey carried out in all families, family trees were formed and the possible genetics pattern was determined on the basis of Cyrilic 3 pedigree program. A complete ophthalmologic examination was conducted over 518 people in 168 families and those family members who had tropia, phoria or microtropia and ≥ 3 PD hypermetropiawere recorded. According to the pedigree analysis, it was determined that the majority of the cases were sporadic (53.2%; 63.6%; 57.1%) in all of the accomodative ET, partial accomodative ET and infantile ET groups while poligenic andmultifactorial genetic pattern (20.1%; 21.8%; 19.1%) was mostly demonstrated in families in which a genetic pattern could be identified. No significant difference was found between strabismus subtypes and genetic patterns (p= 0.682). The frequency of consanguineous marriages among parents of proband parents was 18.1% in the accommodative ET group, 22.6% in the partial accommodative ET group and 14.3% in the infantile ET group. No significant differences were observed between strabismus subtypes and frequency of consanguineous marriages and between the presence of consanguineous marriages and genetic pattern type (p=0.652). As a result of the family tree analysis, the prevalence of strabismus in any relative of the proband was found to be 59% in the accomodative ET group; 45.5% in the partial accomodative ET group, 38.1% in the congenital ET group and no meaningful difference was found among esotropia subtypes (p= 0.077). The prevalence of strabismus in primary relatives was found to be 58.9% in the accomodative ET group, 45.5% in the partial accomodative ET group and 42.8% in the congenital ET group.No statistically significant difference was found among esotropia subtypes (p=0.07). It was also found out that the prevalence of strabismus in proband's relatives on the basis of family history was %35,3 in the accomodative ET group; 20% in the partial accomodative ET group, 28.6% in the congenital ET group and no significant difference was found among esotropia subtypes (p=0.113). The prevalence of strabismus in proband's mother was found to be 25% in the accomodative ET group, 15.4% in the partial accomodative group and 23.1% in the congenital ET group in the examined cases. No statistical difference was found among esotropia subtypes (p=0.462).In the examined cases, the prevalence of strabismus in proband's father was found to be 26.7% in the accomodative ET group, 12.8% in the partial accomodative group whereas strabismus was not identified in any of the cases' fathers in the congenital ET group. The rate in the accomodative ET group was found to be significantly high (p=0.027).The prevalance of strabismus in brothers of the examined cases for accomodative ET, partial ET and congenital ET groups were found to be 23.3% (n=27), 15.4% (n=6) and 15.4% (n=2) respectively. No significant differences were observed among the esotropia subtypes (p=0.101).≥ 3PD hypermetropia frequency in the examined cases' first-degree relativeswas found to be 18.1% (n=21) in the accomodative ET group, 5.2% (n=2) in the partial accomodative ET group and 7.7% (n=1) in the congenital ET group while no meaningful difference was found among esotropia subtypes (p=0.113). According to family tree drawings, one individual in 20.5% of the cases' relatives (n=44), two individuals in 14.9% (n=32), three individuals in 10.2% (n=22) and ≥4 individuals in 8.3% of the cases' relatives were affected; no significant difference was found between esotroia subtypes and the number of family members diagnosed with strabismus (p=0.569). In the pedigree analysis, DNA was isolated from individuals selected from two families found to have strabismus in different individuals in each generation, and single nucleotide differences were investigated in the mutation regions with reference numbers rs34042358, rs2074877, rs12103825, rs61745304, rs61745305, rs20774873 rs17690195, rs61745306, rs rs62060459, rs117809599 and rs4791401 identified in 3rd, 25th, 27th, 29th and 30th exon localizations of the MYH 13 gene. G/A mutation stemming from single nucleotide difference causing missense mutation of MYH13 gene's 25th exon was identified in 8 out of 9 individuals in the first family while one individual did not demonstrate mutation in this region (A/A genotype), as for the other exon regions no mutation which resulted in a change of meaningwas found in any of the individuals. In the second family, G/A mutation due to single nucleotide change causing missense mutation was found in the 25th exon (rs2074877) in four individuals whereas two individuals did not demonstrate mutation in this region (A/A genotype). G/A mutation as a result of single nucleotide difference causing missense mutation in the 29th exon (rs17690195)was identified in 2 individuals while other individuals did not demonstrate mutation in this region (G/G genotype); as for the other exon regions, no mutation which resulted in a change of meaningwas found in any of the individuals. It is thought that G/A mutation resulting from single nucleotide change causing missense mutation in MYH13 gene's 25th exon (rs2074877) may serve asa reference for larger population studies to be conducted in the future, though not specific to accomodative esotropia.