Analysis of genotype-phenotype correlation for GJB2 in 221 non-syndromic deafness probands and their pedigrees / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To assess the possible genotype-phenotype correlation for GJB2.</p><p><b>METHODS</b>Retrospectively analyzed GJB2 gene mutations with non-syndromic hearing impairment (NSHI) patients and their families audiological data. Individuals were grouped, according to non-truncated mutant (non-truncating, NT) and truncating mutations (truncating, T), into T/T group, T/NT group and NT/NT group. And according to whether they carry 235delC, grouped into 235delC/235delC group, 235delC/Non-235del group and Non-235delC/Non-235delC group.</p><p><b>RESULTS</b>Grouped according to whether the truncation mutants:Fisher exact statistical analysis showed that the degree of hearing loss among the three groups did not meet the random distribution (P = 0.003) , T/T group was significantly higher than T/NT group (P = 0.000) and NT/NT group (P = 0.000) on the degree of hearing loss. Grouped according to whether they carry 235delC mutation: degrees of hearing loss among the three groups were statistically significant differences. Respectively pairwise comparisons (Fisher exact test) found 235delC/235delC group was significantly higher than 235delC/Non-235delC on the degree of hearing loss group (P = 0.001) and Non-235delC/Non-235delC group (P = 0.000), 235delC/Non-235delC group higher than Non-235delC/Non-235delC group (P = 0.033). In GJB2 mutations homozygous and compound heterozygous mutation genotype:G109A/G109A, 235delC/512insAACG, 299delAT/G109A and 235delC/G109A degree of hearing loss caused by genotype was significantly lower than 235delC/235delC group.</p><p><b>CONCLUSIONS</b>235delC homozygotes have significantly more hearing impairment, when compared with 235delC/non-235delC compound heterozygotes. People with two non-235delC mutations have even less hearing impairment. Patients with non-truncation mutants (G109A) suffer from lighter hearing loss than truncation mutations(235delC, 299delAT).</p>

Peri-operative management on juvenile recurrent respiratory papillomatosis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the safety of peri-operative management on children with juvenile recurrent respiratory papilloma (JORRP).</p><p><b>METHODS</b>A retrospective analysis was conducted on preoperative assessment, anesthesia methods and options, operative procedure, and postoperative airway maintenance in 28 JORRP children aged from ten months to seven years old. A total of 148 times of surgery was performed on these 28 children.</p><p><b>RESULTS</b>One hundred and nine JORRP children graded one and two-degree dyspnea underwent surgery within 24 hours and were intubated successfully in the first attempt after intravenous induction. Thirty-nine emergency operations were performed in the children graded three and four-degree dyspnea, 35 of them were intubated successfully in the first attempt after inhalation induction and 4 succeeded in the second attempt. No complications occurred in 129 JORRP children postoperatively, 17 children suffered from mild dyspnea and relieved after oxygen inhalation, 2 children were intubated and sent to intensive care unit because of postoperative hypoxemia. All JORRP children got through the peri-operative period safely. The quality of pronunciation in 101 children improved markedly and 35 suffered from slight hoarseness on the 1st postoperative day. Three children had the tracheal tube of tracheostomy removed after receiving five, four and three operations respectively. Nineteen children were followed up for 2 - 5 years. Among them, one child did not relapse 3 years after surgical management.One child suffered from laryngostenosis postoperatively. No death occurred.</p><p><b>CONCLUSION</b>Complete preoperative preparation, rational anesthesia methods, careful operative procedure and airway maintenance after surgery could increase the safety for children with recurrent respiratory papilloma.</p>

Characterization of two Chinese families with aminoglycoside-induced and nonsyndromic hearing loss both carrying a mitochondrial 12S rRNA 1494C>T mutation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of mitochondrial DNA(mtDNA) secondary mutations, haplotypes, GJB2 gene mutations on phenotype of 1494C>T mutation, and to study the molecular pathogenic mechanism of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss.</p><p><b>METHODS</b>Two Chinese Han pedigrees of maternally transmitted aminoglycoside induced and nonsyndromic hearing loss were collected. The two probands and their family members underwent clinical, genetic and molecular evaluations including audiological examinations and mutational analysis of mitochondrial genome and GJB2 gene.</p><p><b>RESULTS</b>Clinical evaluation revealed wide range of severity, age-at-onset and audiometric configuration of hearing impairment in matrilineal relatives in both families, for which the penetrance of hearing loss was respectively 42.9% and 28.6% when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss were 14.3% and 14.3%. Sequence analysis of mitochondrial genomes identified a known 12S rRNA 1494C>T mutation, in addition with distinct sets of mtDNA polymorphisms belonging to Eastern Asian haplogroups C4a1a and B4b1c, respectively.</p><p><b>CONCLUSION</b>Mitochondrial 12S rRNA 1494C>T mutation probably underlie the deafness in both families. Lack of significant mutation in the GJB2 gene ruled out involvement of GJB2 in the phenotypic expression. However, aminoglycosides and other nuclear modifier genes may still modify the phenotype of the 1494C>T mutation in these families. The B4b1c is a newly identified haplogroup in aminoglycoside-induced and nonsyndromic hearing loss family carrying the 1494C>T mutation. The 1494C>T mutation seems to have occurred sporadically through evolution.</p>

Maternally inherited aminoglycoside-induced and nonsyndromic hearing loss in five Han Chinese pedigrees / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the effect of the mitochondrial 12S rRNA mutations on aminoglycoside-induced and nonsyndromic hearing loss, to carry out the clinical and molecular characterization of five Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss.</p><p><b>METHODS</b>Five pedigrees of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss were collected, genomic DNA was extracted, and complete mitochondrial genomes and the gap junction protein beta 2 (GJB2) gene were amplified and sequenced.</p><p><b>RESULTS</b>Clinical evaluation revealed a wide range of severity, age-at-onset and audiometric configuration of hearing impairment in the matrilineal relatives in these families. The penetrance rates of hearing loss in these pedigrees were 17.6%, 50.0%, 66.7%, 31.3% and 23.1%, with an average of 37.7%, when aminoglycoside-induced deafness was included. Sequence analysis of the complete mitochondrial genomes in these pedigrees identified the known 1555A>G mutation and distinct sets of mitochondrial DNA(mtDNA) polymorphisms belonging to Eastern Asian haplogroups D4b2b, B4c1b1, F3, C1 and D5a, respectively. Of these variants, ND1 L89T and CO3 A200T mutations resided at the highly conservative regions. However, there were no functionally significant mutations in tRNAs and rRNAs or secondary known mutations. No hearing loss related GJB2 gene mutation was observed.</p><p><b>CONCLUSION</b>The lack of significant mutation in the ruled out the possible involvement of GJB2 in the phenotypic expression of the 1555A>G mutation in those affected subjects. However, aminoglycosides, mtDNA variations and other nuclear modifier genes may play an important role in the phenotypic manifestation of the 1555A>G mutation in these Chinese families.</p>