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We recently described a novel missense variant [c.2090T>G:p.(Leu697Trp)] in the MYO3Agene, found in two Brazilian families with late-onset autosomal dominant nonsyndromic hearing loss (ADNSHL). Since then, with the objective of evaluating its contribution to ADNSHL in Brazil, the variant was screened in additional 101 pedigrees with probable ADNSHL without conclusive molecular diagnosis. The variant was found in three additional families, explaining 3/101 (~3%) of cases with ADNSHL in our Brazilian pedigree collection. In order to identify the origin of the variant, 21 individuals from the five families were genotyped with a high-density SNP array (~600 K SNPs— Axiom Human Origins; ThermoFisher). The identity by descent (IBD) approach revealed that many pairs of individuals from the different families have a kinship coefficient equivalent to that of second cousins, and all share a minimum haplotype of ~607 kb which includes the c.2090T>G variant suggesting it probably arose in a common ancestor. We inferred that the mutation occurred in a chromosomal segment of European ancestry and the time since the most common ancestor was estimated in 1100 years (CI = 775–1425). This variant was also reported in a Dutch family, which shares a 87,121 bp haplotype with the Brazilian samples, suggesting that Dutch colonists may have brought it to Northeastern Brazil in the 17th century. Therefore, the present study opens new avenues to investigate this variant not only in Brazilians but also in European families with ADNSHL.

Mutations in the CEACAM6gene were first described as causing autosomal dominant nonsyndromic hearing loss, but two splice-altering variants have been recently described as causing autosomal recessive nonsyndromic hearing loss. We describe the novel and extremely rare loss-of-function variant c.436 C > T/p.(Arg146Ter) in the CEACAM16gene segregating with post-lingual progressive autosomal recessive hearing loss. This variant is predicted to significantly reduce the size of the wild type protein. Our results give additional support that loss-of-function variants in CEACAM16cause autosomal recessive hearing loss in humans.

The aim of this study was to search for evidence of stem or progenitor cells in the adult human cochlea by testing for sphere formation capacity and the presence of the stem cell marker ABCG2.

Hereditary nonsyndromic deafness is an autosomal recessive condition in about 80% of cases, and point mutations in the GJB2gene (connexin 26) and two deletions in the GJB6gene (connexin 30), del(GJB6-D13S1830) and del(GJB6-D13S1854), are reported to account for 50% of recessive deafness. Aiming at establishing the frequencies of GJB2mutations and GJB6deletions in the Brazilian population, we screened 300 unrelated individuals with hearing impairment, who were not affected by known deafness related syndromes.

We describe an apparently new genetic syndrome in six members of a family living in a remote area in Northeastern Brazil. This syndrome comprises: short stature due to a marked decrease in the length of the lower limbs predominantly mesomelic with fibular agenesismarked hypoplasia, grossly malformeddeformed clubfeet with severe oligodactyly, upper limbs with acromial dimples and variable motion limitation of the forearms andor hands, severe nail hypoplasiaanonychia sometimes associated with mild brachydactyly and occasionally with preaxial polydactyly. This syndrome is apparently distinct from the syndrome of brachydactylyectrodactyly with fibular aplasia or hypoplasia OMIM 113310, the syndrome of fibular aplasia or hypoplasia, femoral bowing and poly, syn, and oligodactyly OMIM 228930, and from other previously described conditions exhibiting fibular agenesishypoplasia. © 2008 WileyLiss, Inc.

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

We report an autosomal recessive neurodegenerative disorder in 25 white members from a large inbred Brazilian family, 22 of whom were evaluated clinically. This condition is characterized by (1) subnormal vision secondary to apparently nonprogressive congenital optic atrophy; (2) onset of progressive spastic paraplegia in infancy; (3) onset of progressive motor and sensory axonal neuropathy in late childhood/early adolescence; (4) dysarthria starting in the third decade of life; (5) exacerbated acoustic startle response; and (6) progressive joint contractures and spine deformities. Motor handicap was severe, and all patients were wheelchair bound after 15 years old. We performed a genome‐wide screen including 25 affected individuals and 49 of their unaffected relatives. Linkage was detected at 11q13 region with a maximum logarithm of odds score of +14.43, obtained with marker D11S1883. The candidate region, which lies between D11S1908 and D11S1889, encompasses ∼4.8Mb and has more than 100 genes and expressed sequences. We propose the acronym SPOAN (spastic paraplegia, optic atrophy, and neuropathy) for this complex syndrome. Ann Neurol 2005;57:730–737

•Amplification restores auditory input and reduce tinnitus annoyance.•THI reduction has been considered to be clinically and statistically significant (20 or more points) after 6-months of hearing aids usage.•A significant reduction in THI and VAS indicates a significant improvement in tinnitus severity.•Minimal masking levels showed statistically significant reduction after 6-months use of HAs, and inverse correlation with duration of tinnitus.•THI, HHIA, VAS for tinnitus annoyance and MMLs are interrelated parameters on tinnitus amelioration.

ABSTRACTIn this work, we demonstrate that the fosIgene encodes a predicted small protein with 134 amino acids and determines reduced susceptibility to fosfomycin. It raised the MIC from 0.125 to 6 μg/ml when the pBRA100 plasmid was introduced into Escherichia coliTOP10 and to 16 μg/ml when the gene was cloned into the pBC_SK(−) vector and expressed in E. coliTOP10.