title: 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.
authors.affiliation: Istituto di Chimica Biologica, Universita' di Urbino, Urbino, Italy. torroni@axcasp.caspur.it
authors.forename: A
authors.initials: A
authors.lastname: Torroni
authors.forename: F
authors.initials: F
authors.lastname: Cruciani
authors.forename: C
authors.initials: C
authors.lastname: Rengo
authors.forename: D
authors.initials: D
authors.lastname: Sellitto
authors.forename: N
authors.initials: N
authors.lastname: López-Bigas
authors.forename: R
authors.initials: R
authors.lastname: Rabionet
authors.forename: N
authors.initials: N
authors.lastname: Govea
authors.forename: A
authors.initials: A
authors.lastname: López De Munain
authors.forename: M
authors.initials: M
authors.lastname: Sarduy
authors.forename: L
authors.initials: L
authors.lastname: Romero
authors.forename: M
authors.initials: M
authors.lastname: Villamar
authors.forename: I
authors.initials: I
authors.lastname: del Castillo
authors.forename: F
authors.initials: F
authors.lastname: Moreno
authors.forename: X
authors.initials: X
authors.lastname: Estivill
authors.forename: R
authors.initials: R
authors.lastname: Scozzari
mesh_terms: D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length; D012335:RNA, Ribosomal / Q000235:genetics*; D013030:Spain
chemical_list: D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S