Analysis of genetic characteristics in two Chinese children of type Ⅱ Waardenburg syndrome / 中华耳鼻咽喉头颈外科杂志

Objective: To screen and analyze the mutations of MITF gene in two children of type Ⅱ Waardenburg syndrome (WS2) from different families in Yunnan,China,and to explore the possible molecular pathogenesis. Methods: With informed consent, medical history collection, physical examinations, audiological evaluation, and high resolution computer tomography (HRCT) scan of temporal bone were performed on the two WS2 probands and their family members. Genomic DNA was extracted from peripheral blood of all individuals. The coding regions including all exons, part of introns and promoters of MITF, PAX3, SOX10, SNAI2, END3, ENDRB, and KITLG genes were sequenced by high-throughput sequencing. According to the results of high-throughput sequencing, pathogenic mutations detected in the probands and their parents were verified by Sanger sequencing. Results: The proband 1 carried c.641_643delGAA mutation in the 7th exon of MITF gene, which was a frame-shift mutation resulting in an amino acid change of p.214delR. It was a de novo mutation as the parents of proband 1 showed no variation on this site. The proband 2 carried heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene, which defected the function of MITF protein. Conclusion: Genetic examinations provide important evidence for diagnosis of Waardenburg syndrome. Heterozygous mutation c.641_643delGAA and heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene might be the molecular pathogenesis of the two WS2 probands in this study.

Identification and genetic analysis of new mutations in EYA1 gene of BOS syndrome / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the clinical manifestations of a patient with branchiootic syndrome(BOS) and her families and to carry out genetic testing in order to specify the biological pathogenesis. Methods: Clinical data of the patient and her families were collected. Genomic DNA in the peripheral blood of the proband and her family members was extracted. All exons of 406 deafness-related susceptible genes as well as their flanking regions were sequenced by high-throughput sequencing, and the mutation sites of the proband and her parents were validated by Sanger sequencing. Results: There were nine members in three generations, of whom four presented with hearing loss, preauricular fistula and branchial fistula which met the diagnostic criteria of BOS. Proband and her mother presented with auricle malformation and inner ear malformation. And no one had abnormalities in the kidneys of all the patients. Pedigree analysis revealed that the mode of inheritance in the family was consistent with the autosomal dominant pattern. Mutational analysis showed that all the affected patients detected a heterozygous frameshift variation c.1255delT in the EYA1 gene, which had not been reported. Genotype and phenotype were co-isolated in this family. Such a frameshift variation produced a premature termination codon, thereby causing premature termination of translation (p.C419VFS*12). ACMG identified that the mutation was pathogenic. This mutation was novel and not detected in controls. A heterozygous missense variation mutation c.403G>A(p.G135S) in EYA1 gene was also detected in three members of this family. ACMG identified that the mutation clinical significance was uncertain. However, two of whom were normal, which seemed the disease was not caused by this mutation in this family. Conclusions: A novel frameshift mutation in EYA1(c.1255delT) is the main molecular etiology of BOS in the Chinese family. This study expands the mutational spectrum of EYA1 gene. The clinical manifestations are heterogeneous among patients in this family. The diagnosis of BOS should combine gene tests with clinical phenotypes analysis.

Long-term therapeutic effects of tracheotomy on children with recurrent laryngeal papillomatosis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To explore the long-term therapeutic effects of tracheotomy on juvenile onset recurrent respiratory papillomatosis in children.</p><p><b>METHODS</b>Between 1993 and 2007, 86 cases of juvenile onset recurrent respiratory papillomatosis (JRRP) in children were encounted and divided into tracheotomy group and conventional surgery group, the clinical data of these children were retrospectively analyzed.</p><p><b>RESULTS</b>There were 29 cases in tracheotomy group, the time of carrying tracheal casing pipe was 13 - 66.5 months, the operative times of every case was 4 - 9 times (median 7), there were 27 cases with more than 2 years release after extubation. There were 2 cases with tumor dissemination into incision of trachea and endotracheal, one case lost to follow up and the other one dead. No case developed laryngotracheal stenosis and severe complication. There were 57 cases in conventional surgery group, the operation times of every case was 9 - 32 times (median 18). Fifty-three cases with no recurrence after follow up for more than one year; 2 cases with trachea tumor dissemination, and after operation, no recurrence after 2 years follow up. Two cases with endotracheal dissemination, one case lost to follow up and the other one dead. No case developed laryngotracheal stenosis and severe complication. The voice assessment result of tracheotomy group was obviously better than that in the conventional surgery group, the difference had statistical significance (χ(2) = 33.16, P < 0.005), the tumor dissemination rate of the two groups had no statistical significance (χ(2) = 0.0026, P > 0.05).</p><p><b>CONCLUSIONS</b>Tracheotomy significantly reduce the operative times, give the greatest degree of preservation of laryngeal function, and it do not increase the tumor dissemination into trachea. Tracheotomy is an effective method of treatment in children with a high rate of recurrence, and with poor economic conditions, and difficult to follow-up. It can improve the long-term life quality of the children.</p>