We studied a family presenting 10 individuals affected by autosomal dominant deafness in all freq... more We studied a family presenting 10 individuals affected by autosomal dominant deafness in all frequencies and three individuals affected by high frequency hearing loss. Genomic scanning using the 50k Affymetrix microarray technol-ogy yielded a Lod Score of 2.1 in chromosome 14 and a Lod Score of 1.9 in chromosome 22. Mapping refinement us-ing microsatellites placed the chromosome 14 candidate region between markers D14S288 and D14S276 (8.85 cM) and the chromosome 22 near marker D22S283. Exome sequencing identified two candidate variants to explain hear-ing loss in chromosome 14 [PTGDR – c.G894A:p.R298R and PTGER2 – c.T247G:p.C83G], and one in chromosome 22 [MYH9, c.G2114A:p.R705H]. Pedigree segregation analysis allowed exclusion of the PTGDR and PTGER2 vari-ants as the cause of deafness. However, the MYH9 variant segregated with the phenotype in all affected members, except the three individuals with different phenotype. This gene has been previously described as mutated in autosomal...
We hereby report on the audiological and genetic findings in individuals from a Brazilian family,... more We hereby report on the audiological and genetic findings in individuals from a Brazilian family, with the following mitochondrial mutation A1555G in the 12SrRNA gene (MT-RNR-1). Nine individuals underwent speech, audiologic (tonal audiometry and logoaudiometry) and genetic evaluations. Eight individuals among the A1555G carriers were affected by hearing impairment and one person had normal hearing thresholds till the end of the present study. The audiologic evaluation results indicated normal hearing thresholds all the way to bilateral profound hearing loss with post-lingual onset and variable configuration. Two affected siblings presented progressive hearing loss. It was impossible to precise the time of hearing loss onset; however, the impairment was present in both children and adults. The genetic study revealed the A1555G mitochondrial mutation in the 12SrRNA gene. Given the prevalence of mitochondrial mutations as a cause of hearing loss, it is fundamental to perform the etiop...
Mitochondrial mutations are responsible for at least 1% of the cases of hereditary deafness, but ... more Mitochondrial mutations are responsible for at least 1% of the cases of hereditary deafness, but the contribution of each mutation has not yet been defined in African-derived or native American genetic back- grounds. A total of 203 unselected hearing-impaired patients were screened for the presence of the mitochondrial mutation A1555G in the 12S rRNA gene and mutations in the tRNASer(UCN)
... A novel autosomal dominant deafness locus (DFNA58) maps to 2p12-p21. K Lezirovitz,; MCC Braga... more ... A novel autosomal dominant deafness locus (DFNA58) maps to 2p12-p21. K Lezirovitz,; MCC Braga,; RS Thiele-Aguiar,; MTBM Auricchio,; PL Pearson,; PA Otto,; RC Mingroni-Netto. ... WT, Yang T, Smith RJ, Van Camp G. Autosomal dominant nonsyndromic hearing impairment. ...
SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by ou... more SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with...
We studied a family presenting 10 individuals affected by autosomal dominant deafness in all freq... more We studied a family presenting 10 individuals affected by autosomal dominant deafness in all frequencies and three individuals affected by high frequency hearing loss. Genomic scanning using the 50k Affymetrix microarray technol-ogy yielded a Lod Score of 2.1 in chromosome 14 and a Lod Score of 1.9 in chromosome 22. Mapping refinement us-ing microsatellites placed the chromosome 14 candidate region between markers D14S288 and D14S276 (8.85 cM) and the chromosome 22 near marker D22S283. Exome sequencing identified two candidate variants to explain hear-ing loss in chromosome 14 [PTGDR – c.G894A:p.R298R and PTGER2 – c.T247G:p.C83G], and one in chromosome 22 [MYH9, c.G2114A:p.R705H]. Pedigree segregation analysis allowed exclusion of the PTGDR and PTGER2 vari-ants as the cause of deafness. However, the MYH9 variant segregated with the phenotype in all affected members, except the three individuals with different phenotype. This gene has been previously described as mutated in autosomal...
We hereby report on the audiological and genetic findings in individuals from a Brazilian family,... more We hereby report on the audiological and genetic findings in individuals from a Brazilian family, with the following mitochondrial mutation A1555G in the 12SrRNA gene (MT-RNR-1). Nine individuals underwent speech, audiologic (tonal audiometry and logoaudiometry) and genetic evaluations. Eight individuals among the A1555G carriers were affected by hearing impairment and one person had normal hearing thresholds till the end of the present study. The audiologic evaluation results indicated normal hearing thresholds all the way to bilateral profound hearing loss with post-lingual onset and variable configuration. Two affected siblings presented progressive hearing loss. It was impossible to precise the time of hearing loss onset; however, the impairment was present in both children and adults. The genetic study revealed the A1555G mitochondrial mutation in the 12SrRNA gene. Given the prevalence of mitochondrial mutations as a cause of hearing loss, it is fundamental to perform the etiop...
Mitochondrial mutations are responsible for at least 1% of the cases of hereditary deafness, but ... more Mitochondrial mutations are responsible for at least 1% of the cases of hereditary deafness, but the contribution of each mutation has not yet been defined in African-derived or native American genetic back- grounds. A total of 203 unselected hearing-impaired patients were screened for the presence of the mitochondrial mutation A1555G in the 12S rRNA gene and mutations in the tRNASer(UCN)
... A novel autosomal dominant deafness locus (DFNA58) maps to 2p12-p21. K Lezirovitz,; MCC Braga... more ... A novel autosomal dominant deafness locus (DFNA58) maps to 2p12-p21. K Lezirovitz,; MCC Braga,; RS Thiele-Aguiar,; MTBM Auricchio,; PL Pearson,; PA Otto,; RC Mingroni-Netto. ... WT, Yang T, Smith RJ, Van Camp G. Autosomal dominant nonsyndromic hearing impairment. ...
SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by ou... more SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with...
Uploads
Papers by Karina Lezirovitz