The A1555G Mutation in the 12S rRNA Gene of Human mtDNA: Recurrent Origins and Founder Events in Families Affected by Sensorineural Deafness

Abstract

The mtDNA variation of 50 Spanish and 4 Cuban families affected by nonsyndromic sensorineural deafness due to the A1555G mutation in the 12S rRNA gene was studied by high-resolution RFLP analysis and sequencing of the control region. Phylogenetic analyses of haplotypes and detailed survey of population controls revealed that the A1555G mutation can be attributed to >/=30 independent mutational events among the 50 Spanish families and that it occurs on mtDNA haplogroups that are common in all European populations. This indicates that the relatively high detection rate of this mutation in Spain is not due to sampling biases or to a single major founder event. Moreover, the distribution of these mutational events on different haplogroups is compatible with a random occurrence of the A1555G mutation and tends to support the conclusion that mtDNA backgrounds do not play a significant role in the expression of the mutation. Overall, these findings appear to indicate that the rare detection of this mutation in other populations is most likely due to inadequacy in patient ascertainment and molecular screening. This probable lack of identification of the A1555G mutation in subjects affected by sensorineural hearing loss implies that their maternally related relatives are not benefiting from presymptomatic detection and information concerning their increased risk of ototoxicity due to aminoglycoside treatments.

Mitochondrial DNA mutations in patients with postlingual, nonsyndromic hearing impairment

“…This leaves two possible explanations for the discordance: environmental factors, such as unrecorded aminoglycoside use, A1555G being a known ototoxic risk factor, 43 or else other genetic factors, that is, multiple founder effects or systematic selection (A1555G being found in different mtDNA haplogroups 41 ). An unbiased evaluation of the population prevalence of A1555G in different European countries can perhaps address this issue.…”

Mitochondrial DNA variability in Russians and Ukrainians: Implication to the origin of the Eastern Slavs

“…In addition to the populations mentioned above, data from the following populations were used : 42 Middle Easterners and 69 Sardinians (Di Rienzo & Wilson, 1991) ; 45 Israeli Druze (Macaulay et al 1999) ; 85 Algerians and 54 Portuguese (Co# rte- ; 18 Berbers and 56 Canary Islanders (Pinto et al 1996) ;139 Spanish (Co# rteReal et al 1996 ;Pinto et al 1996 ;Torroni et al 1999) ; 105 Basques (Bertranpetit et al 1995 ;Co# rte-Real et al 1996) ; 22 Turks, 29 Finns, 33 Danes, 107 Northern Germans, 49 Bavarians ; 32 Russian Germans from a German community in western Siberia (Baranov et al 1999) ; 73 Finns and 28 Swedes (Kittles et al 1999) ; 261 British (Piercy et al 1993 ;Richards et al 1996) ; 70 individuals from the eastern Italian Alps (Stenico et al 1996) ; 205 subjects from central Asian admixed populations of East Asian and European ancestry : 55 Kazakh, 95 Kirghiz, 55 Uighur (Comas et al 1998) ; 300 individuals from India . HVS I sequences of the Ossetians, Georgians, and Armenians from the Caucasus, represented in the form of median networks , were also analysed.…”

Genetic susceptibility to aminoglycoside ototoxicity: How many are at risk?

“…[1][2][3][5][6][7][8][9][10][11][12][13][14]16 Those data suggest that the mutation has occurred multiple times and in several lineages throughout human history, that it is not an uncommon cause of hearing loss, and that a variety of populations may be at risk. Combined, those data suggest that the seemingly rare detection of the A1555G mutation may represent more of an ascer-tainment bias than a scarcity of the mutation itself, and that the frequency of this mutation in US populations warrants further study.…”

“…Combined, those data suggest that the seemingly rare detection of the A1555G mutation may represent more of an ascer-tainment bias than a scarcity of the mutation itself, and that the frequency of this mutation in US populations warrants further study. 1,2,[5][6][7][8][9][10][11][12][13][14]16 Similar data for the 961delT ϩ C(n) mutation are lacking.…”