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Background: Congenital deafness is one of the most distressing disorders affecting humanity and exhibits a high incidence worldwide. Most cases of congenital deafness in the Chinese population are caused by defects in a limited number of genes. A convenient and reliable method for detecting common deafness-related gene mutations in the Chinese population is required. Methods: We developed a PCR-reverse dot blot (RDB) assay for screening 20 hotspot mutations of GJB2, GJB3, SLC26A4, and MT-RNR1, which are common non-syndromic hearing loss (NSHL)–associated genes in the Chinese population. The PCR-RDB assay consists of multiplex PCR amplifications of 10 fragments in the target sequence of the four above-mentioned genes in wild-type and mutant genomic DNA samples followed by hybridization to a test strip containing allele-specific oligonucleotide probes. We applied our method to a set of 225 neonates with deafness gene mutations and 30 normal neonates. Results: The test was validated through direct sequencing in a blinded study with 100% concordance. Conclusions: The results demonstrated that our reverse dot blot assay is a reliable and effective genetic screening method for identifying carriers and individuals with NSHL among the Chinese population. [ABSTRACT FROM AUTHOR]

We report a novel mutation (HBB: c.268_281delAGTGAGCTGCACTG) in a Chinese proband, who was also an α-thalassemia (α-thal) Southeast Asian (αα/– –SEA) deletion carrier and displayed characteristic hematological features of β-thalassemia (β-thal) traits. The proband and carriers in her family presented hematological abnormalities. This novel mutation results in a frameshift and consequently creates a premature stop codon at codon 90 of theHBBgene. Thus, couples at-risk for β-thal should also be tested for this mutation. Double heterozygotes for α- and β-thal are easily misdiagnosed as pure β-thal carriers, which should be noted in the process of risk assessment and counseling. [ABSTRACT FROM AUTHOR]

We report a novel mutation on the α2-globin gene,HBA2: c.184A>T, detected in a Chinese proband. This mutation resulted in a Lys→Term substitution at position 62 of the α2-globin gene, causing a premature termination of translation. This mutation did not cause severe hematological abnormalities in the carriers. From the properties of substituted residues on the α2-globin gene, it is generally expected that this mutation causes unstable and truncated protein, thus this mutation should be detected in couples at-risk for α-thalassemia (α-thal). [ABSTRACT FROM AUTHOR]

Objectives To explore the pathogenic causes of a proband who was diagnosed with non-syndromic hearing loss. Methods We performed targeted capture of 159 known deafness-related genes and next-generation sequencing in the proband who was tested negative for the twenty hotspot variants in four common deafness-related genes( GJB2 , GJB3 , SLC26A4 and MTRNR1 ); Clinical reassessments, including detailed audiological and ocular examinations were performed in the proband and his normal parents. Results We identified a novel heterozygous variant of CDH23 :c.4567A > G (p.Asn1523Asp) in exon 37 (NM_022124), in conjunction with a reported mutation of CDH23 :c.5101G > A (p.Glu1701Lys) in exon 40, to be a potentially pathogenic compound heterozygosity in the proband. The unaffected father has a heterozygous variant of CDH23 :c.4567A > G, and the normal mother has another heterozygous variant, CDH23 :c.5101G > A. The novel variant was absent in the 1000 Genomes Project. The clinical reassessments revealed binaural profound sensorineural hearing loss (DFNB12) without retinitis pigmentosa in the proband. Conclusions This study demonstrates that the novel variant c.4567A > G (p.Asn1523Asp) in compound heterozygosity with c.5101G > A (p. Glu1701Lys) in the CDH23 gene is the main cause of DFNB12 in the proband. Simultaneously, this study provides a foundation to further elucidate the CDH23 -related mechanisms of DFNB12. [ABSTRACT FROM AUTHOR]