Ozgul et al. (2011) studied 8 patients with retinitis pigmentosa who were found to have mutations in the MAK gene (see MOLECULAR GENETICS). The age at diagnosis in 3 patients was in the third decade of life, whereas ... Ozgul et al. (2011) studied 8 patients with retinitis pigmentosa who were found to have mutations in the MAK gene (see MOLECULAR GENETICS). The age at diagnosis in 3 patients was in the third decade of life, whereas the other 5 patients were diagnosed in the fourth through sixth decades of life. Visual acuity was relatively preserved, with 6 of the 8 patients having 20/40 acuity in at least 1 eye. Visual fields appeared to be more severely affected: half of the patients experienced tunnel vision of 25 degrees or less. Overall, patients with MAK mutations seemed to have a disease course that was somewhat less rapid and less severe than that observed in a number of other genetic forms of RP (see 268000).
Tucker et al. (2011) performed exome sequencing in a patient of Jewish ancestry with autosomal recessive retinitis pigmentosa and identified homozygosity for a 353-bp Alu insertion in the MAK gene (154235.0001). Screening of 1,798 unrelated individuals with autosomal ... Tucker et al. (2011) performed exome sequencing in a patient of Jewish ancestry with autosomal recessive retinitis pigmentosa and identified homozygosity for a 353-bp Alu insertion in the MAK gene (154235.0001). Screening of 1,798 unrelated individuals with autosomal recessive RP identified 20 additional probands who were homozygous for the same Alu insertion; 2 affected relatives were also found to be homozygous for the Alu insertion, whereas 5 unaffected relatives were not. All 21 families with the Alu insertion reported Jewish ancestry, although there was no known consanguinity. In 1 family, the unaffected mother had emigrated from Turkey, whereas the unaffected father had emigrated from Russia, suggesting that the founder of the mutation may have lived before the separation of the Sephardic and Ashkenazi groups in the Middle Ages. Tucker et al. (2011) noted that although MAK was originally described as a testis-enriched gene, human fertility appeared to be unaffected by loss of MAK function as the majority of individuals with MAK-associated RP in their study each had 2 or more children. Ozgul et al. (2011) performed whole-exome sequencing in a 31-year-old Turkish woman with RP, born of first-cousin parents, who was negative for mutation in known RP genes. They identified homozygosity for a nonsense mutation in the MAK gene (154235.0002) that segregated with disease in the family and was not found in 130 Turkish controls. Whole-genome SNP analysis in 334 isolated or autosomal recessive RP patients of Dutch, Italian, Israeli, and Palestinian origin revealed 11 probands with a large homozygous region encompassing the MAK gene; homozygous missense mutations in MAK were identified in 3 of the probands (154235.0003-154235.0005). Direct sequencing of coding exons and splice junctions of the MAK gene in an additional 93 Dutch isolated or autosomal recessive RP patients revealed 1 proband with compound heterozygosity for missense mutations; however, the patient's sister, who was of uncertain disease status, also carried both mutations. Another patient was found to be heterozygous for a missense mutation; although no second mutation could be found, RNA analysis indicated lack of an RNA product from the second allele. Ozgul et al. (2011) noted that because all reported MAK mutations are shared by both retinal- and testis-enriched isoforms, it was possible that mutations in this gene could affect spermatogenesis.