Objective To explore the genetic mutation in neonates who failed to pass hearing screening.Methods A total of 111 cases of neonates who failed to pass hearing screening and were conifrmed sensorineural deafness by auditory brainstem evoked potential (ABR) were randomly selected. The heel blood was collected and DNA was extracted.GJB2, SLC26A4, and 11 mutation hotspots in mitochondria gene12SrRNA were tested. The relationship between degree of hearing loss and gene mutation was analyzed.Results In 111 neonates, mutation in deafness gene were found in 24 cases (21.6%) . Among them 14 cases (12.6%) hadGJB2 gene mutation including 5 cases of 235delC single heterozygous mutation, 5 cases of 235delC, and 1 case each of 299_300delAT compound heterozygous mutation, 235delC homozygous mutation, 299_300delAT single heterozygous mutation, 176_191del16 and 235delC compound heterozygous mutation, and 299_300delAT and 508_511dupAACG compound heterozygous mutation respectively. Ten cases (9.0%) hadSLC26A4 gene mutation including 2 cases of IVS7-2A>G single heterozygous mutation, 3 cases of 1226G>A single heterozygous mutation, 2 cases of 2168A>G single heterozygous mutation, and 3 cases of IVS7-2A>G and 2168A>G compound heterozygous mutation. Mitochondrial gene mutations were not detected. Conclusions Deafness gene mutation is detected in more than 1/5 neonates who failed to pass newborn hearing screening. GJB2 gene mutation is the most commons. The implementation of hotspots deafness gene detection can improve the diagnostic rate of deafness.

Substances addiction is one of the important factors that deeply affect human health.At present, there is still lack of effective treatment drugs in the clinic.Exploring mechanisms of substances addiction, finding new therapeutic targets and developing effective therapeutic drugs are important issues to be solved.Hyperpolarization-activated cyclic nucleotide gated cation channels (HCN channels) participate in many advanced brain activities and are closely related to the occurrence and progression of various brain diseases.Among them, the researches on the role and mechanism of HCN channels in substances addiction are gradually gaining attention.Reviewing the researches regarding substances addiction, abnormal function and abnormal expression of HCN channels were observed in many brain regions under the condition of psychoactive substances addiction.However, it has not yet been able to fully understand the mechanism and the behavioral consequences of this change.Therefore, we review the neurobiological mechanisms of HCN channels in substances addiction induced by opioids, cocaine, cannabis, amphetamines, alcohol and tobacco, in order to provide new ideas for the mechanism researches and treatment of substance addiction.

OBJECTIVETo explore the molecular basis for three pedigrees affected with hypophosphatemia vitamin D resistant rickets (X-linked hypophosphatemia, XLH).

METHODSPeripheral blood samples from the three pedigrees were collected. Following DNA extraction, the 11 exons and flanking regions of the PHEX gene were subjected to PCR amplification and direct sequencing. Pathogenicity of identified mutations was evaluated through genotype-phenotype correlation.

RESULTSFor pedigrees 1 and 2, pathogenic mutations were respectively identified in exon 8 (c.871C>T, p.R291X) and exon 15 (c.1601C>T, p.P534L) of the PHEX gene. For pedigree 3, a novel mutation (c.1234delA, p.S412Vfs*12) was found in exon 11 of the PHEX gene, which caused shift the reading frame and premature termination of protein translation.

CONCLUSIONThe three mutations probably account for the XLH in the affected pedigrees. The discovery of novel mutations has enriched the spectrum of PHEX gene mutations.

OBJECTIVE: To detect pathogenic variants in a pedigree affected with propionic acidemia (PA). METHODS: The proband was subjected to high-throughput next-generation sequencing. Suspected variants were validated by Sanger sequencing of his family members. mRNA was extracted from peripheral blood lymphocytes from the proband's father in order to verify the impact of the splicing variant by RT-PCR combined with Sanger sequencing. The pathogenicity of the missense variant was predicted by using PolyPhen-2, Mutation Taster, SIFT, COBALT and HOPE software. RESULTS: The proband was found to harbor compound heterozygous variants of the PCCB gene, namely c.184-2A>G and c.733G>A (p.G245S), which were respectively inherited from his father and mother. RT-PCR combined with Sanger sequencing confirmed skipping of exon 2 during transcription. Bioinformatic analysis indicated the c.733G>A (p.G245S) variant to be damaging. CONCLUSION The two variants of the PCCB gene probably underlay the disease in this patient. Above findings have enriched the spectrum of PCCB gene variants.
Exons ; Humans ; Mutation ; Mutation, Missense ; Pedigree ; Propionic Acidemia/genetics*