dc.creatorLEZIROVITZ, Karina
dc.creatorPARDONO, Eliete
dc.creatorAURICCHIO, Maria T. B. de Mello
dc.creatorSILVA, Fernando L. de Carvalho e
dc.creatorLOPES, Juliana J.
dc.creatorABREU-SILVA, Ronaldo S.
dc.creatorROMANOS, Jihane
dc.creatorBATISSOCO, Ana C.
dc.creatorMINGRONI-NETTO, Regina C.
dc.date.accessioned2012-10-20T03:06:50Z
dc.date.accessioned2018-07-04T15:33:20Z
dc.date.available2012-10-20T03:06:50Z
dc.date.available2018-07-04T15:33:20Z
dc.date.created2012-10-20T03:06:50Z
dc.date.issued2008
dc.identifierEUROPEAN JOURNAL OF HUMAN GENETICS, v.16, n.1, p.89-96, 2008
dc.identifier1018-4813
dc.identifierhttp://producao.usp.br/handle/BDPI/27729
dc.identifier10.1038/sj.ejhg.5201917
dc.identifierhttp://dx.doi.org/10.1038/sj.ejhg.5201917
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1624373
dc.description.abstractNonsyndromic autosomal recessive deafness accounts for 80% of hereditary deafness. To date, 52 loci responsible for autosomal recessive deafness have been mapped and 24 genes identified. Here, we report a large inbred Brazilian pedigree with 26 subjects affected by prelingual deafness. Given the extensive consanguinity found in this pedigree, the most probable pattern of inheritance is autosomal recessive. However, our linkage and mutational analysis revealed, instead of an expected homozygous mutation in a single gene, two different mutant alleles and a possible third undetected mutant allele in the MYO15A gene (DFNB3 locus), as well as evidence for other causes for deafness in the same pedigree. Among the 26 affected subjects, 15 were homozygous for the novel c.10573delA mutation in the MYO15A gene, 5 were compound heterozygous for the mutation c.10573delA and the novel deletion c.9957_9960delTGAC and one inherited only a single c.10573delA mutant allele, while the other one could not be identified. Given the extensive consanguinity of the pedigree, there might be at least one more deafness locus segregating to explain the condition in some of the subjects whose deafness is not clearly associated with MYO15A mutations, although overlooked environmental causes could not be ruled out. Our findings illustrate a high level of etiological heterogeneity for deafness in the family and highlight some of the pitfalls of genetic analysis of large genes in extended pedigrees, when homozygosity for a single mutant allele is expected.
dc.languageeng
dc.publisherNATURE PUBLISHING GROUP
dc.relationEuropean Journal of Human Genetics
dc.rightsCopyright NATURE PUBLISHING GROUP
dc.rightsclosedAccess
dc.subjectautosomal recessive deafness
dc.subjectDFNB3 locus
dc.subjectMYO15A gene
dc.titleUnexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness
dc.typeArtículos de revistas


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