RESUMEN
BACKGROUND: Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene mutations, and hearing loss is the most frequent phenotypic feature. This study aimed at identifying the causative gene mutation for a three-generation Chinese family with HDR syndrome and analyzing auditory phenotypes in all familial HDR syndrome cases. METHODS: Three affected family members underwent otologic examinations, biochemistry tests, and other clinical evaluations. Targeted genes capture combining next-generation sequencing was performed within the family. Sanger sequencing was used to confirm the causative mutation. The auditory phenotypes of all reported familial HDR syndrome cases analyzed were provided. RESULTS: In Chinese family 7121, a heterozygous nonsense mutation c.826C>T (p.R276*) was identified in GATA3. All the three affected members suffered from sensorineural deafness and hypocalcemia; however, renal dysplasia only appeared in the youngest patient. Furthermore, an overview of thirty HDR syndrome families with corresponding GATA3 mutations revealed that hearing impairment occurred earlier in the younger generation in at least nine familial cases (30%) and two thirds of them were found to carry premature stop mutations. CONCLUSIONS: This study highlights the phenotypic heterogeneity of HDR and points to a possible genetic anticipation in patients with HDR, which needs to be further investigated.
Asunto(s)
Factor de Transcripción GATA3/genética , Pérdida Auditiva Sensorineural/genética , Hipoparatiroidismo/genética , Nefrosis/genética , Niño , Femenino , Genotipo , Pérdida Auditiva/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Mutación/genética , LinajeRESUMEN
CONCLUSION: To our knowledge, this is the first report of PJVK gene mutation in a Chinese non-syndromic sensorineural hearing loss (NSHL) family. Our data indicate that the PJVK gene contributes to hearing impairment in the Chinese population, but it is not a major cause. OBJECTIVE: To investigate the contribution of PJVK mutations to NSHL in the Chinese population. METHODS: We screened for the PJVK gene in a sample of 65 autosomal recessive NSHL families without GJB2, SLC26A4, or mitochondrial 12S rRNA gene mutations. Seven pairs of PCR primers were designed to amplify all of the exons and their flanking regions of the PJVK gene. The PCR products were sequenced and analyzed for identification of mutations. RESULTS: In all, we identiï¬ed one novel frameshift mutation, c.930_931del AC (p.C312W fsX19), co-segregating with the phenotype in one consanguineous family with a prevalence of 1.5% (1/65). The p.C312W fsX19 mutation was just positioned in the zinc-fingers domain, which was important to the function of pejvakin, and resulted in a stop codon after 19 additional amino acids. It was not identiï¬ed in the controls and was considered as the causative mutation of family 804566 with autosomal recessive, non-syndromic, prelingual sensorineural hearing impairment.
Asunto(s)
Pérdida Auditiva Sensorineural/genética , Proteínas del Tejido Nervioso/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , Conexina 26 , Conexinas , Mutación del Sistema de Lectura , HumanosRESUMEN
CONCLUSIONS: The majority of the patients with unilateral auditory neuropathy spectrum disorder (UANSD) were pediatric and mostly showed a great degree of hearing loss when diagnosed. Abnormal auditory brainstem response (ABR) and preserved otoacoustic emissions (OAEs) and/or cochlear microphonics (CM) were important features to differentiate it from common sensorineural deafness and central nerve hearing loss. OBJECTIVE: To identify the clinical characteristics of patients with UANSD. METHODS: This was a retrospective study involving 14 patients diagnosed as having UANSD between 2004 and 2010 in the Chinese PLA Hospital. RESULTS: In all, 50% of the cases were males (1:1 sex ratio) and the average age of onset was 4.1 years. Of the 14 affected ears with UANSD in these cases, 6 were left-sided, while 8 were right-sided. Of the 14 contralateral ears, 4 presented with sensorineural hearing loss, while the other 10 showed normal hearing. The degree of hearing loss in the 14 affected ears varied, including moderate in 1, moderately severe in 4, severe in 5, and profound in 4. ABRs were absent in the 14 affected ears, while the OAEs, and/or CM were present.