Objective: Hereditary nonsyndromic deafness is an autosomal recessive condition in about 80% of cases, and point mutations in the GJB2 gene (connexin 26) and two deletions in the GJB6 gene (connexin 30), del(GJB6-D13S1830) and del(GJB6-D13S1854), are reported to account for 50% of recessive deafness. Aiming at establishing the frequencies of GJB2 mutations and GJB6 deletions in the Brazilian population, we screened 300 unrelated individuals with hearing impairment, who were not affected by known deafness related syndromes. Methods:We firstly screened the most frequently reported mutations, c.35delG and c.167delT in the GJB2 gene, and del(GJB6-D13S1830) and del(GJB6-D13S1854) in the GJB6 gene, through specific techniques. The detected c.35delG and c.167delT mutations were validated by sequencing. Other mutations in the GJB2 gene were screened by single-strand conformation polymorphism and the coding region was sequenced when abnormal patterns were found.

We describe laryngeal malformations and voice disorders in two new patients with the autosomal recessive Richieri-Costa and Pereira form of acrofacial dysostosis. This report confirms the data on the first five patients we had already presented in 1996.

Laryngeal structural anomalies were described in 13 cases of Richieri-Costa Pereira syndrome, and four previously reported cases were reviewed. The 17 individuals examined had the typical laryngeal anomalies and vocal disorders previously described. The new findings are the laryngeal microweb observed in three cases and arytenoid anteriorization movement observed in 14 cases.

We report on laryngeal malformations in 5 subjects, 4 females and 1 male, with the autosomal-recessive Richieri-Costa and Pereira form of acrofacial dysostosis. Characteristics of the voice are described.

Background Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. Methods We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti–RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. Results We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. Conclusions This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs.

Mani pulation of auditory stimuli affect the ABR evoked potentials and aid the diagnosis, particularly in auditory neuropathy patients. Some patients with auditory neuropathy lose evoked otoacoustic emissions over time; in these cases, comparing responses to rarefaction and condensation clicks, and decreasing the stimulus rate can show an extended cochlear microphonism or yield an improved electric potential record. Aim: To analyze the effect of these click manipulations on the records of potentials of patients with hearing loss as a form of improving the diagnosis. Study design: A clinical prospective study. Patients and Method: 59 patients with hearing loss underwent ABR recording using rarefaction and condensation clicks at a stimulus rate of 27.7/sec, and rarefaction clicks at a stimulus rate of 3.3/sec. The records were compared to the otoacoustic evoked emission. Results: Eight (13.53%) patients showed changes in the recorded ABR potentials as a result of manipulating the characteristics of clicks, such as extended cochlear microphonism or an improved record of electric potentials. Five patients had no otoacoustic evoked emissions. Conclusion: Manipulation of click stimuli can improve the topographic diagnosis of hearing loss, particularly in the group of auditory neuropathy patients with no otoacoustic evoked emissions, where usually, the diagnosis is only possible through the method described above.

The cause of hearing impairment has not been elucidated in a large proportion of patients. We screened by 1-Mb array-based comparative genomic hybridization (aCGH) 29 individuals with syndromic hearing impairment whose clinical features were not typical of known disorders. Rare chromosomal copy number changes were detected in eight patients, four de novo imbalances and four inherited from a normal parent. The de novo alterations define candidate chromosome segments likely to harbor dosage-sensitive genes related to hearing impairment, namely 1q23.3-q25.2, 2q22q23, 6p25.3 and 11q13.2-q13.4. The rare imbalances also present in normal parents might be casually associated with hearing impairment, but its role as a predisposition gene remains a possibility. Our results show that syndromic deafness is frequently associated with chromosome microimbalances (14-27%), and the use of aCGH for defining disease etiology is recommended.

Here we describe a novel missense variant in the KCNQ4 gene and a private duplication at 7q31.1 partially involving two genes (IMMP2L and DOCK4). Both mutations segregated with nonsyndromic hearing loss in a family with three affected individuals. Initially, we identified the duplication in a screening of 132 unrelated cases of hearing loss with a multiplex ligation-dependent probe amplification panel of genes that are candidates to have a role in hearing, including IMMP2L. Mapping of the duplication by array-CGH revealed that the duplication also encompassed the 3′-end of DOCK4. Subsequently, whole-exome sequencing identified the breakpoint of the rearrangement, thereby confirming the existence of a fusion IMMP2L-DOCK4 gene. Transcription products of the fusion gene were identified, indicating that they escaped nonsense-mediated messenger RNA decay. A missense substitution (c.701A4T) in KCNQ4 (a gene at the DFNA2A locus) was also identified by whole-exome sequencing. Because the substitution is predicted to be probably damaging and KCNQ4 has been implicated in hearing loss, this mutation might explain the deafness in the affected individuals, although a hypothetical effect of the product of the fusion gene on hearing cannot be completely ruled out.