Expression of LATS1 in head and neck squamous cell carcinoma and its effect on tumor cell proliferation and invasion.

Nowadays, the incidence and mortality of head and neck tumors are gradually increasing. Head and neck malignant tumors (such as laryngeal cancer, hypopharyngeal cancer, oral cancer, nasopharyngeal cancer, oropharyngeal cancer, and other head and neck malignancies) are more common among systemic tumors. The most common pathological head and neck tumor type is squamous cell carcinoma, accounting for about 90%. In this study, immunohistochemical methods were used to collect the normal squamous epithelial tissues of the head and neck, atypical hyperplasia tissues, and head and neck squamous cell carcinomas on a tissue chip for detection. The recombinant LATS1 overexpression plasmid was prepared and transferred into B88 cells. Western blotting, MTT, and Transwell chamber methods were used to detect the effects of LATS1 proliferation, migration, and B88 cell overexpression. The experimental results showed that in head and neck squamous cell carcinoma, the expression of LATS1 protein decreased from 59.3% to 11.3%. At the same time, this protein inhibited the proliferation, migration, and invasion of head and neck squamous epithelial cells and also inhibited epithelium- Interstitial transformation exerts its tumor suppressor effect, indicating that LATS1 may play a tumor suppressor effect as a tumor suppressor gene. An in-depth study of the role and mechanism of LATS1 protein in the occurrence of head and neck squamous cell carcinoma may provide new opportunities for the treatment of head and neck squamous cell carcinoma in the future.

SIRT4 expression in laryngeal squamous cell carcinoma.

SIRT4 has been reported to be abnormally expressed in many malignant tumor tissues, but data in laryngeal squamous cell carcinoma (LSCC) is lacking. In the present study, we detected the expression of SIRT4 in 168 pairs of LSCC tissues and adjacent normal tissues using RT-qPCR, immunoblotting and immunohistochemical staining, and analyzed its clinical implication. We found that SIRT4 expression was low in LSCC tissues, and was significantly related to histological grade, T classification, clinical stage, lymph node metastasis and recurrence of LSCC patients. In vitro, knockdown of SIRT4 promoted the proliferation and migration of LSCC cells, while overexpression of SIRT4 inhibits the proliferation and migration of LSCC cells. Moreover, the expression of SIRT4 protein was an independent factor affecting the disease-free survival (DFS) (HR=0.562, 95%CI=0.1290.834) and overall survival rates (OS) (HR=0.628, 95%CI=0.267-0.935) of LSCC patients. The 5-years DFS and OS in LSCC patients with low SIRT4 expression were significantly lower than that in LSCC patients with high SIRT4 expression. In conclusion, SIRT4 was lowly expressed in LSCC patients, which might be related to more aggressive tumor behaviour and a poor prognosis.

A follow-up study of a Chinese family with Waardenburg syndrome type II caused by a truncating mutation of MITF gene.

BACKGROUND: Waardenburg syndrome (WS) is a highly clinically and genetically heterogeneous disease. The core disease phenotypes of WS are sensorineuronal hearing loss and pigmentary disturbance, which are usually caused by the absence of neural crest cell-derived melanocytes. At present, four subtypes of WS have been defined, which are caused by seven genes. Waardenburg syndrome type 2 (WS2) is one of the most common forms. Two genes, MITF and SOX10, have been found to be responsible for majority of WS2. METHODS: In this study, we performed a clinical longitudinal follow-up and mutation screening for a Chinese family with Waardenburg syndrome type II. RESULTS: A diversity of clinical manifestations was observed in this WS2 family. In addition to the congenital hearing loss of most affected family members, progressive hearing loss was also found in some WS2 patients. A nonsense mutation of c.328C>T (p.R110X) in MITF was identified in all affected family members. This mutation results in a truncated MITF protein, which is considered to be a disease-causing mutation. CONCLUSION: These findings offer a better understanding of the spectrum of MITF mutations and highlight the necessity of continuous hearing assessment in WS patients.

Efficacy of microsurgery in combined with topical-PDT in treating recurrent respiratory papillomatosis: compare JORRP with AORRP.

Background: Recurrent respiratory papillomatosis (RRP) remains a challenging and frustrating disease to treat.Objective: To explore the efficacy of microsurgery in combined with Topical-PDT in treating recurrent respiratory papillomatosis.Materials and methods: Fifty patients with RRP were treated with microsurgery in combined with Topical-PDT. Medical document of each patient was retrospectively reviewed. Detailed clinical information, metrics of clinical course, and current results were evaluated.Results: Juvenile onset RRP (JORRP) might experience a more aggressive course than AORRP (adult onset RRP) with higher Derkay score (p < .01) and higher operation frequency per year (p < .01). Microsurgical excision combined with Topical-PDT every 25 days achieved "remission" of disease in 78% of patients, "clearance" of disease in 52%, and "Cured" in two patients. Each patient who achieved "remission" of disease, performed 6.82 ± 3.39 operations, and continued 8.93 ± 7.03 months of treatment duration. No statistically differences were found in these two aspects between JORRP and AORRP. A negative correlation between tracheotomy and the efficacy of microsurgery in combined with Topical-PDT was found (p = .025, Pearson's r = -0.3).Conclusions and significance: Microsurgery in combined with Topical-PDT might be a powerful method to treat RRP. Tracheotomy is a negative factor for this therapy.

Immune defense is the primary function associated with the differentially expressed genes in the cochlea following acoustic trauma.

Our previous RNA-sequencing analysis of the rat cochlear genes identified multiple biological processes and molecular pathways in the cochlear response to acoustic overstimulation. However, the biological processes and molecular pathways that are common to other species have not been documented. The identification of these common stress processes is pivotal for a better understanding of the essential response of the cochlea to acoustic injury. Here, we compared the RNA-sequencing data collected from mice and rats that sustained a similar, but not identical, acoustic injury. The transcriptome analysis of cochlear genes identified the differentially expressed genes in the mouse and rat samples. Bioinformatics analysis revealed a marked similarity in the changes in the biological processes between the two species, although the differentially expressed genes did not overlap well. The common processes associated with the differentially expressed genes are primarily associated with immunity and inflammation, which include the immune response, response to wounding, the defense response, chemotaxis and inflammatory responses. Moreover, analysis of the molecular pathways showed considerable overlap between the two species. The common pathways include cytokine-cytokine receptor interactions, the chemokine signaling pathway, the Toll-like receptor signaling pathway, and the NOD-like receptor signaling pathway. Further analysis of the transcriptional regulators revealed common upstream regulators of the differentially expressed genes, and these upstream regulators are also functionally related to the immune and inflammatory responses. These results suggest that the immune and inflammatory responses are the essential responses to acoustic overstimulation in the cochlea.

Tension-relaxing method-A simplified revision of the endoscopic septoplasty technique: For both aesthetic appearance and functionality.

OBJECTIVE: This article describes a simplified endonasal approach compared with traditional techniques for the correction of crooked noses by using endoscopic tension-relaxing septoplasty in the absence of nasal splints, with attempts to improve both the aesthetic appearance and functionality. STUDY DESIGN: A retrospective study was conducted at our institution with all 26 patients who underwent tension-relaxing rhinoseptoplasty by endoscope between November 2008 and January 2013. METHODS: Patients who were concerned about their aesthetic appearance and nasal obstruction were subjected to anterior rhinoscopy, endoscopic examination of the nasal cavity, and computed tomography for the evaluation of correlations among deformity of the nasal structures and nasal airway. The tension-relaxing method was used in the endoscopic rhinoseptoplasty by an endonasal approach. We introduced this technique in the surgery for patients with a C- or an I-shaped crooked nose. Subjective (visual analog scale) and objective (quantitative electronic meter measurement) assessments were used to evaluate aesthetic appearance. Validated Nasal Obstruction Symptom Evaluation scale and active anterior rhinomanometry were used to assess nasal obstruction. RESULTS: All the patients indicated cosmetic satisfaction and reduced nasal obstruction. In cases with I-shaped and C-shaped crooked nose deformities, pre- and postoperative angle values (mean ± standard deviation) were 13.35 ± 3.36° versus 1.85 ± 1.66° (n = 15) and 153.69 ± 6.48° versus 176.64 ± 2.32° (n = 11), respectively. Postoperative correction rates were statistically significant (p < 0.001) in both groups. Results from active anterior rhinomanometry indicated significant improvement in objective nasal obstruction from a mean baseline value of 0.56 ± 0.07 Pa/cm(3)/s (range, 0.43- 0.69 Pa/cm(3)/s), to a 12-month value of 0.26 ± 0.02 Pa/cm(3)/s (range, 0.23-0.29 Pa/cm(3)/s) (p < 0.001). The mean rhinoseptoplasty duration time was 19.00 ± 3.53 minutes. The nose deformities were significantly improved, with no recurrences of septal deviation or crooked nose, nor complications of septal perforation and nasal infection 12 months after the operation. CONCLUSION: This simple technique is feasible and minimally invasive, and may be particularly beneficial to patients with a deviated septum who seek to improve both their aesthetic appearance and nasal functionality. However, this method is not appropriate for those with a crooked nose caused by nasal bone deformity, lateral cartilages, and severe septal deformity.

Variation analysis of transcriptome changes reveals cochlear genes and their associated functions in cochlear susceptibility to acoustic overstimulation.

Individual variation in the susceptibility of the auditory system to acoustic overstimulation has been well-documented at both the functional and structural levels. However, the molecular mechanism responsible for this variation is unclear. The current investigation was designed to examine the variation patterns of cochlear gene expression using RNA-seq data and to identify the genes with expression variation that increased following acoustic trauma. This study revealed that the constitutive expressions of cochlear genes displayed diverse levels of gene-specific variation. These variation patterns were altered by acoustic trauma; approximately one-third of the examined genes displayed marked increases in their expression variation. Bioinformatics analyses revealed that the genes that exhibited increased variation were functionally related to cell death, biomolecule metabolism, and membrane function. In contrast, the stable genes were primarily related to basic cellular processes, including protein and macromolecular syntheses and transport. There was no functional overlap between the stable and variable genes. Importantly, we demonstrated that glutamate metabolism is related to the variation in the functional response of the cochlea to acoustic overstimulation. Taken together, the results indicate that our analyses of the individual variations in transcriptome changes of cochlear genes provide important information for the identification of genes that potentially contribute to the generation of individual variation in cochlear responses to acoustic overstimulation.

Molecular profile of cochlear immunity in the resident cells of the organ of Corti.

BACKGROUND: The cochlea is the sensory organ of hearing. In the cochlea, the organ of Corti houses sensory cells that are susceptible to pathological insults. While the organ of Corti lacks immune cells, it does have the capacity for immune activity. We hypothesized that resident cells in the organ of Corti were responsible for the stress-induced immune response of the organ of Corti. This study profiled the molecular composition of the immune system in the organ of Corti and examined the immune response of non-immune epithelial cells to acoustic overstimulation. METHODS: Using high-throughput RNA-sequencing and qRT-PCR arrays, we identified immune- and inflammation-related genes in both the cochlear sensory epithelium and the organ of Corti. Using bioinformatics analyses, we cataloged the immune genes expressed. We then examined the response of these genes to acoustic overstimulation and determined how changes in immune gene expression were related to sensory cell damage. RESULTS: The RNA-sequencing analysis reveals robust expression of immune-related genes in the cochlear sensory epithelium. The qRT-PCR array analysis confirms that many of these genes are constitutively expressed in the resident cells of the organ of Corti. Bioinformatics analyses reveal that the genes expressed are linked to the Toll-like receptor signaling pathway. We demonstrate that expression of Toll-like receptor signaling genes is predominantly from the supporting cells in the organ of Corti cells. Importantly, our data demonstrate that these Toll-like receptor pathway genes are able to respond to acoustic trauma and that their expression changes are associated with sensory cell damage. CONCLUSION: The cochlear resident cells in the organ of Corti have immune capacity and participate in the cochlear immune response to acoustic overstimulation.

Clinical effect analysis of microscopic surgery for epiglottis cysts with coblation.

This study aims to explore the effects and advantages of coblation combined with microscopy to treat epiglottis cysts. Ninety patients with epiglottis cysts were randomly assigned to three groups: the first group: marsupialisation + electric coagulation group, n = 30; the second group: marsupialisation + coblation, n = 30; and the third group: marsupialisation + coblation + microsurgery, n = 30. To compare the cure rate, intraoperative bleeding volume, postoperative pain, operation time and postoperative complications were investigated among these three groups. The comparison among three procedures showed a significant difference for intraoperative bleeding volume, operation time and postoperative pain (P < 0.05), whereas no significant difference was observed for cure rate (P > 0.05). These three procedures are effective in treating epiglottis cysts. Microscopic surgery with coblation has the advantages of less bleeding, short procedure duration, less pain and few complications. Thus, microscopic surgery is worthy of clinical application.

Genetic and phenotypic heterogeneity in Chinese patients with Waardenburg syndrome type II.

Waardenburg Syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss and pigmentary abnormalities of the eyes, hair, and skin. Microphthalmia-associated transcription factor (MITF) gene mutations account for about 15% of WS type II (WS2) cases. To date, fewer than 40 different MITF gene mutations have been identified in human WS2 patients, and few of these were of Chinese descent. In this study, we report clinical findings and mutation identification in the MITF gene of 20 Chinese WS2 patients from 14 families. A high level of clinical variability was identified. Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients. Five affected individuals (5/20, 25.0%) had numerous brown freckles on the face, trunk, and limb extremities. Mutation screening of the MITF gene identified five mutations: c.20A>G, c.332C>T, c.647_649delGAA, c.649A>G, and c.763C>T. The total mutational frequency of the MITF gene was 21.4% (3/14), which is significantly higher than the 15.0% observed in the fair-skinned WS2 population. Our results indicate that MITF mutations are relatively common among Chinese WS2 patients.

Phenotype and genotype analysis of a Chinese family with prelingual X-linked hereditary hearing impairment.

BACKGROUND: X-linked hearing impairment is clinically and genetically a heterogeneous disease. Although many disorders manifest with hearing loss, a limited number of sex-linked loci and only one gene (POU3F4) have been shown to be implicated in X-linked non-syndromic hearing impairment. In the present study, we have performed a clinical and genetic analysis of a Chinese family with X-linked non-syndromic hearing loss, with emphasis on audiological findings and genomic mapping. METHODS: The clinical features of Family JX01 were evaluated by physical and audiometric examination in eighteen family members. Mutation screening of POU3F4 was identified by polymerase chain reaction (PCR) amplification and sequencing. Molecular evaluation consisted of X-chromosome wide genotyping by microsatellite makers (STR), followed by analyzing using MLINK computer program. RESULTS: Five affected males demonstrated bilateral, symmetrical sensorineural and profound hearing loss. The hearing impairment started prelingual. The female carriers did not have any complain of hearing loss, however, two of them were tested with milder loss with high frequency. No causative mutations in POU3F4 gene were detected by DNA sequencing. Linkage analysis indicated that the responsible gene was linked to locus DXS1227 (maximum lod score = 2.04 at theta = 0). CONCLUSIONS: The affected males in Family JX01 have profound prelingual sensorineural hearing impairment. In addition, two female carriers showed mild to moderate hearing losses. However, none of females complained of any hearing loss. Analysis of hereditary deafness in this family mapped most compatibly to the Xq27.2.

Mutations at position 7445 in the precursor of mitochondrial tRNA(Ser(UCN)) gene in three maternal Chinese pedigrees with sensorineural hearing loss.

We report here the clinical, genetic and molecular characterization of three Chinese pedigrees with nonsyndromic bilateral hearing loss. Clinical and genetic evaluations revealed the variable severity and age-of-onset in hearing impairment in these families. Strikingly, there were extremely low penetrances of hearing impairment in these Chinese families. Sequence analysis of the complete mitochondrial DNA (mtDNA) showed the known A7445C mutation in two pedigrees and the novel A7445T mutation in another pedigree, in addition to distinct sets of mtDNA polymorphisms belong to Asian haplogroups D4j and F4. Indeed, the A7445C or A7445T mutation in the CO1 and the precursor of tRNA(Ser(UCN)) genes was present in homoplasmy only in the maternal lineage of those pedigrees but not other members of these families and 164 Chinese controls. In fact, the A7445C or A7445T mutation results in a read-through of the stop condon AGA of the CO1 message on the H strand of mtDNA, thereby adding three amino acids (Ser-Gln-Lys) to the C-terminal of the polypeptide. However, the mutated polypeptide may retain a partial function. Alternatively, the A7445C or A7445T mutation is adjacent to the site of 3' end endonucleolytic processing of L-strand RNA precursor, spanning tRNA(Ser(UCN)) and ND6 mRNA. Thus, the A7445C or A7445T mutation may also cause a defect in the processing of the L-strand RNA precursor, thus causing mitochondrial dysfunctions. Furthermore, the occurrence of the mutations at position 7445 in these genetically unrelated subjects affected by hearing impairment strongly indicates that mutations at the position 7445 are involved in the pathogenesis of hearing impairment.

[Mutation screening of MITF gene in patients with Waardenburg syndrome type 2].

Warrgenburg syndrome type 2 (WS2) is the most common autosomal dominantly-inherited syndrome with hearing loss. MITF (microphthalmia associated transcription factor)is a basic-helix-loop-helix-luecine zipper (bHLHZip) factor which regulates expression of tyrosinase, and is involved in melanocyte differentiation. Mutations in MITF associated with WS2 have been identified in some but not all affected families. Here, we report a three-generation Chinese family with a point mutation in the MITF gene causing WS2. The proband exhibits congenital severe sensorineural hearing loss, heterochromia iridis and facial freckles. One of family members manifests sensorineural deafness, and the other patients show premature greying or/and freckles. This mutation, heterozygous deletion c.639delA, creates a stop codon in exon 7 and is predicted to result in a truncated protein lacking normal interaction with its target DNA motif. This mutation is a novel mutation and the third case identified in exon 7 of MITF in WS2. Though there is only one base pair distance between this novel mutation and the other two documented cases and similar amino acids change, significant difference is seen in clinical phenotype, which suggests genetic background may play an important role.

[Expression and significance of TGF-beta1 and HSP70 in human laryngeal squamous cell carcinoma].

OBJECTIVE: To investigate the expression of TGF-beta1 and HSP70 in human laryngeal squamous cell carcinoma. METHOD: The expression levels of TGF-beta1 and HSP70 in 53 specimens of human laryngeal squamous cell carcinoma and 48 specimens of para-carcinoma were detected by immuno- histochemistry and computer assisted image analysis. RESULT: The expression of TGF-beta1 was decreased in carcinoma tissues compared with para-carcinoma tissues ( P < 0.05), while the expression of HSP70 was increased ( P < 0.05). Both the expression of TGF-beta1 and HSP70 were significantly correlated with the differentiation of laryngeal squamous cell carcinoma (P < 0.01 or P < 0.05). However, there was a negative correlation between TGF-beta1 and HSP70 (r = -0.87, P < 0.01). CONCLUSION: TGF-beta1 and HSP70 play an important role in malignant behaviors of human laryngeal carcinoma.

Coexistence of mitochondrial 12S rRNA C1494T and CO1/tRNA(Ser(UCN)) G7444A mutations in two Han Chinese pedigrees with aminoglycoside-induced and non-syndromic hearing loss.

Mutations in mitochondrial DNA are one of the important causes of hearing loss. We report here the clinical, genetic, and molecular characterization of two Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic bilateral hearing loss. Clinical evaluation revealed the wide range of severity, age-at-onset, and audiometric configuration of hearing impairment in matrilineal relatives in these families. The penetrances of hearing loss in these pedigrees were 20% and 18%, when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss in these seven pedigrees were 10% and 15%. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the presence of the deafness-associated 12S rRNA C1494T and CO1/tRNA(Ser(UCN)) G7444A mutations. Their distinct sets of mtDNA polymorphism belonged to Eastern Asian haplogroup C4a1, while other previously identified six Chinese mitochondrial genomes harboring the C1494T mutation belong to haplogroups D5a2, D, R, and F1, respectively. This suggested that the C1494T or G7444A mutation occurred sporadically and multiplied through evolution of the mitochondrial DNA (mtDNA). The absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in their mtDNA suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the 12S rRNA C1494T and CO1/tRNA(Ser(UCN)) G7444A mutations in those Chinese families. However, aminoglycosides and other nuclear modifier genes play a modifying role in the phenotypic manifestation of the C1494T mutation in these Chinese families.

Nonsense mutations in the PAX3 gene cause Waardenburg syndrome type I in two Chinese patients.

BACKGROUND: Waardenburg syndrome type I (WS1) is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmental abnormalities of the eye, hair and skin, and dystopia canthorum. The gene mainly responsible for WS1 is PAX3 which is involved in melanocytic development and survival. Mutations of PAX3 have been reported in familiar or sporadic patients with WS1 in several populations of the world except Chinese. In order to explore the genetic background of Chinese WS1 patients, a mutation screening of PAX3 gene was carried out in four WS1 pedigrees. METHODS: A questionnaire survey and comprehensive clinical examination were conducted in four Chinese pedigrees of WS1. Genomic DNA from each patient and their family members was extracted and exons of PAX3 were amplified by PCR. PCR fragments were ethanol-purified and sequenced in both directions on an ABI_Prism 3100 DNA sequencer with the BigDye Terminator Cycle Sequencing Ready Reaction Kit. The sequences were obtained and aligned to the wild type sequence of PAX3 with the GeneTool program. RESULTS: Two nonsense PAX3 mutations have been found in the study population. One is heterozygous for a novel nonsense mutation S209X. The other is heterozygous for a previously reported mutation in European population R223X. Both mutations create stop codons leading to truncation of the PAX3 protein. CONCLUSIONS: This is the first demonstration of PAX3 mutations in Chinese WS1 patients and one of the few examples of an identical mutation of PAX3 occurred in different populations.

[Mutation screening of the COCH gene in familial and sporadic patients with late onset nonsyndromic sensorineural hearing loss among Chinese population].

OBJECTIVE: To investigate the mutational of the coagulation factor C homology (COCH) gene related to autosomal dominant sensorineural nonsyndromic hearing loss (DFNA) with late onset in Chinese population. METHODS: Peripheral blood samples were collected from he members of 26 DFNA families, members of 19 small DFNA families with un recognized inheritance pattern, and 22 sporadic patients with sensorineural nonsyndromic late onset hearing loss, the hearing loss of all of which occurred during the age range 10 - 40, and 100 normal controls. From different parts of China, these subjects underwent questionnaire survey too. Genomic DNA was isolated, COCH mutation was screened by PCR and sequencing, and restriction endonuclease analysis was used to detect the mutation sites of the COCH gene. The conservation in evolution of the target amino acid sequences was analyzed using CluatalX1.82 software. RESULTS: DNA sequencing of coding regions and exon/intron boundaries of COCH 2 - 12 exons identified a heterozygous G-to-A substitution at position 1625 in exon 12 in a large DFNA family, leading to a C542Y substitution, and a heterozygous T-to-C substitution at position 1535 in exon 12 in a small family, leading to a M512T substitutions. Both the residues of Cys542 and M512 were conserved across human, mouse, chicken, and zebrafish. These mutations were not detected in the 100 control subjects. CONCLUSION: The C542Y and the M512T mutations cause hearing loss in Chinese DFNA families.

[Mapping of gene underlying autosomal dominant non-syndromic hearing loss(DFNA)].

Hereditary non-syndromic sensorineural hearing loss is a genetically highly heterogeneous group of disorders. To date, at least 50 loci for autosomal dominant non-syndromic sensorineural hearing loss (DFNA) have been identified by linkage analysis. Here we report a huge family with late onset autosomal dominant hereditary non-syndromic hearing loss. In this family, 73 of 170 family members have been conducted physical examination, pure-tone audiometry, immittance testing and auditory brainstem response testing (ABR). The results indicated that 39 of 73 tested family members have sensorineural hearing loss in various degrees. No associated visible abnormalities in other systems were found in this family. After exclusion of the 14 known DFNA loci with markers from the Hereditary Hearing Loss Homepage (URL: http://dnalab-www.uia.ac.be/dnalab/hhh), a genome wide scan was carried out using 382 highly informative microsatellite markers at approximately 9.2 cM intervals throughout the genome. Linkage analysis was carried out under a fully penetrant autosomal dominant mode of inheritance with no phenocopies. A maximum two-point LOD score of 6.69 at theta=0 was obtained for marker D14S1040. Haplotype analysis placed the locus within a 7.6 cM genetic interval defined by marker D14S1021 and D14S70, overlapping with the DFNA9 locus.

[Clinical features of a Chinese pedigree with Waardenburg syndrome type 2].

OBJECTIVE: To investigate detailed clinical features of a Chinese pedigree with Waardenburg syndrome type 2. METHODS: Members of this pedigree were interviewed to identify personal or family medical histories of hearing loss, the use of aminoglycosides, and other clinical abnormalities by filling questionnaire. The audiological and other clinical evaluations of the proband and other members of this family were conducted, including pure-tone audiometry, immittance and auditory brain-stem response and ophthalmological, dermatologic, hair, temporal bone CT examinations. RESULTS: This family is categorized as Waardenburg syndrome type 2 according to its clinical features. It's an autosomal dominant disorder with incomplete penetrance. The clinical features varied greatly among family members and characterized by sensorineural hearing loss, heterochromia irides, freckle on the face and premature gray hair. Hearing loss can be unilateral or bilateral, congenital or late onset in this family. CONCLUSION: This Chinese family has some unique clinical features comparing with the international diagnostic criteria for Waardenburg syndrome. This study may provide some evidences to amend the diagnostic criteria for Waardenburg syndrome in Chinese population.