Using linkage analysis followed by sequencing of the CHX10 gene in two consanguineous Arab families with isolated microphthalmia/clinical anophthalmia (MCOP2) and a Jewish Syrian family with microphthalmia/clinical anophthalmia with colobomas (MCOPCB3), Bar-Yosef et al. (2004) identified homozygosity for three mutations. One of the Arab families was of Palestinian origin and was found to have a 1237G>A transition in exon 4 of the CHX10 gene, resulting in an arg227-to-trp substitution in the CVC domain. Bar-Yosef et al. (2004) noted that this arginine residue is conserved in all known CHX10 homologs as well as in the CVC domains of related genes. The remaining Arab family was found to have an approximately 4-kb deletion encompassing exon 3 of the CHX10 gene, thus abolishing both the homeobox domain and the CVC domain. The third mutation identified in this study was found in the Jewish Syrian family.

Faiyaz-Ul-Haque et al. (2007) carried out a molecular study on two consanguineous families from Qatar affected with microphthalmia/anophthalmia. Affected individuals in both families exhibited non-functional eyes (bilaterally) with very small globes and cloudy corneas. Their cranial and facial features, height and weight were within normal limits, and these patients displayed normal intelligence. Affected and unaffected members of these families were typed for the D14S1047 microsatellite marker, which resides in close vicinity of the CHX10. Haplotypes were constructed and homozygosity analysis was performed assuming an autosomal recessive inheritance. All affected individuals were found to be homozygous, while unaffected parents were found to be heterozygous for the allele. Also, sequencing of the CHX10 gene was performed in this study. Faiyaz-Ul-Haque et al. (2007) identified a homozygous c.599G-C substitution in the fourth exon of the CHX10 gene in the affected individuals. Carrier parents were found to be heterozygous for this change. This mutation produces a p.Arg200Pro substitution in the DNA binding domain of the CHX10. The CHX10 mutations in the Middle Eastern patients and their absence in the European population, led Faiyaz-Ul-Haque et al. (2007) to suggest that the CHX10 defects in microphthalmia/anophthalmia patients of Middle Eastern origin are because of shared ancestry and consanguinity.

In affected members of a consanguineous Jewish Syrian family with microphthalmia/clinical anophthalmia and coloboma of the iris, Bar-Yosef et al. (2004) identified homozygosity for a G-to-A transition in the last base of the first CHX10 intron, predicted to abolish the donor-acceptor site at the intron-exon junction.