The clinical phenotype and gene analysis of syndromic deafness with PTPN11 gene mutation / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the clinical phenotype and screen the genetic mutations of hereditary deafness in three deaf families to clarify their molecular biology etiology. Methods: From January 2019 to January 2020, three deaf children and family members were collected for medical history, physical examination, audiology evaluation, electrocardiogram and cardiac color Doppler ultrasound, temporal bone CT examination, and peripheral blood DNA was obtained for high-throughput sequencing of deafness genes. Sanger sequencing was performed to verify the variant sites among family members. The pathogenicity of the variants was evaluated according to the American College of Medical Genetics and Genomics. Results: The probands in the three families had deafness phenotypes. In family 1, proband had multiple lentigines, special facial features, growth retardation, pectus carinatum, abnormal skin elasticity, cryptorchidism and other manifestations. In family 2, proband had special facial features, growth retardation and abnormal heart, and the proband in family 3 had growth retardation and abnormal electrocardiogram. Genetic testing of three families detected three heterozygous mutations in the PTPN11 gene: c.1391G>C (p.Gly464Ala), c.1510A>G (p.Met504Val), c.1502G>A (p.Arg501Lys). All three sites were missense mutations, and the mutation sites were highly conserved among multiple homologous species. Based on clinical manifestations and genetic test results, proband 1 was diagnosed with multiple lentigines Noonan syndrome, and probands 2 and 3 were diagnosed with Noonan syndrome. Conclusion: Missense mutations in the PTPN11 gene may be the cause of the disease in the three deaf families. This study enriches the clinical phenotype and mutation spectrum of the PTPN11 gene in the Chinese population.

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.

Serum levels of 25-(OH)D(3) and total IgE in children with asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the changes and clinical significance of serum levels of 25-(OH)D(3) and total IgE in children with asthma.</p><p><b>METHODS</b>Thirty children with asthma, 40 children with asthmatic bronchitis, and 40 healthy children were enrolled. Double-antibody radioimmunoassay was used to detect the levels of serum 25-(OH)D(3) and total IgE.</p><p><b>RESULTS</b>Serum 25-(OH)D(3) levels (18±3 ng/Ml)decreased significantly in the asthmatic group compared with those in the asthmatic bronchitis group (43±3 ng/mL) and the control group (43±3 ng/mL) (P<0.01). In contrast, serum total IgE levels (192±16 IU/mL) increased significantly in the asthmatic group compared with those in the asthmatic bronchitis group (123±14 IU/mL) and the control group (118±15 IU/mL) (P<0.01). Serum 25-(OH)D(3) levels were negatively correlated with serum total IgE levels in asthmatic children (r=-0.783, P<0.01). There were no correlation between serum 25-(OH)D(3) levels and serum total IgE level in the asthmatic bronchitis and the control groups.</p><p><b>CONCLUSIONS</b>25-(OH)D(3) may play an important role in the pathogenesis of asthma. The increased serum 25-(OH)D(3) level may inhibit total IgE expression, suggesting that increasing serum 25-(OH)D(3) level might be a new option for the prevention and treatment of asthma.</p>