A Mayan founder mutation is a common cause of deafness in Guatemala

Abstract

SUMMARY Over 5% of the world population have varying degrees of hearing loss. Mutations in GJB2 are the most common cause of autosomal recessive non-syndromic hearing loss (NSHL) in many populations. The frequency and type of mutations are influenced by ethnicity. Guatemala is a multi-ethnic country with four major populations: Maya, Ladino, Xinca, and Garifuna. To determine the mutation profile of GJB2 in a NSHL population from Guatemala, we sequenced both exons of GJB2 in 133 unrelated families. A total of six pathogenic variants were detected. The most frequent pathogenic variant is c.131G>A (p.Trp44*) detected in 21 of 266 alleles. We show that c.131G>A is associated with a conserved haplotype in Guatemala suggesting a single founder. The majority of Mayan population lives in the west region of the country from where all c.131G>A carriers originated. Further analysis of genome-wide variation of individuals carrying the c.131G>A mutation compared to those of Native American, European, and African populations shows a close match with the Mayan population.

High Rates of Three Common GJB2 Mutations c.516G>C, c.-23+1G>A, c.235delC in Deaf Patients from Southern Siberia Are Due to the Founder Effect

“…Specific ethno-geographic prevalence patterns were found for many of them [ 3 , 4 , 5 ]. For instance, variant c.35delG (p.Gly12Valfs*2) is prevalent in deaf patients of Caucasian origin [ 3 , 6 ]; c.235delC (p.Leu79Cysfs*3) is common in some Asian populations [ 4 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]; c.167delT (p.Leu56Argfs*26) is frequent in Ashkenazi Jews [ 15 , 16 ]; c.427C>T (p.Arg143Trp) is specific for population of Ghana (West Africa) and Peru (South America) [ 17 , 18 ]; c.71G>A (p.Trp24*) is widely spread in Indians and European Gypsies [ 19 , 20 , 21 ]; c.109G>A (p.Val37Ile) prevails in populations of Southeast Asia [ 5 ]; the splice donor variant c.-23+1G>A was found in many populations worldwide but extremely high prevalence of c.-23+1G>A was detected among Yakuts (Eastern Siberia, Russia) [ 22 ]; c.131G>A (p.Trp44*) was found with high frequency among descendants of ancestral Mayan population in Guatemala [ 23 ].…”

“…Contribution of the founder effect in extremely high rate of mutation c.-23+1G>A among Yakuts (Eastern Siberia, Russia) was evidenced by the c.-23+1G>A haplotype analysis, and the age of this mutation was estimated at approximately 800 years [ 22 ]. Common haplotype was established for specific mutation c.131G>A (p.Trp44*) found in individuals from Guatemala suggesting a single founder from ancestral Mayan population [ 23 ]. The founder effect was also suggested in high prevalence of mutation c.235delC in East Asians (China, Japan, Korea), Mongolians (Mongolia), and Altaians (Southern Siberia, Russia) but there were only a few studies of the c.235delC-bearing haplotypes to support this hypothesis [ 8 , 9 , 14 , 37 , 38 , 39 ].…”

Unique Mutational Spectrum of the GJB2 Gene and Its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys)

“…Many of them have very specific ethno-geographic prevalence patterns [7,9] being attributed to a founder effect for certain ethnic groups. The variant c.35delG (p.Gly12Valfs*2) is prevalent in deaf patients of Caucasian origin [10,11]; c.235delC (p.Leu79Cysfs*3) is common in East and Southeast Asians [12,13,14]; c.167delT (p.Leu56Argfs*26) is more specific for Ashkenazi Jews [15]; c.427C>T (p.Arg143Trp) was found with high frequency in population of Ghana (West Africa) [16]; c.71G>A (p.Trp24*) is widely distributed in Indians and European Gypsies [17,18,19]; c.109G>A (p.Val37Ile) prevails in populations of Southeast Asia [20]; splice donor variant c.-23+1G>A (originally named IVS1+1G>A) is widespread among Yakuts (Eastern Siberia, Russia) [21]; c.131G>A (p.Trp44*) was found with high frequency among descendants of the ancestral Mayan population in Guatemala [22].…”

Spectrum and Frequency of the GJB2 Gene Pathogenic Variants in a Large Cohort of Patients with Hearing Impairment Living in a Subarctic Region of Russia (the Sakha Republic)

“…Spectrum and allelic frequencies of the GJB2 gene vary significantly among different ethnic groups worldwide [ 3 , 4 ]. Currently, the regions of Europe [ 5 – 32 ], Asia [ 33 – 48 ], the Middle East [ 49 – 56 ], Central and North America [ 57 – 61 ], South America [ 62 – 69 ], Greenland [ 70 ], Australia [ 71 ], and some parts of Africa [ 72 – 81 ] have been characterized according to the pathogenic variant spectrum and frequency of the GJB2 gene. However, data regarding the molecular basis of HI in populations of Russia are scarce [ 7 , 16 , 82 ].…”