OBJECTIVETo achieve early diagnosis for inheritable hearing loss and determine carrier rate of deafness causing gene mutations in order to provide information for premarital, prenatal and postnatal genetic counseling.

METHODSA total of 17 000 dried heel blood spots of normal newborns in Chengdu were collected with informed consent obtained from their parents. Genomic DNA was extracted from dried blood spots using Qiagen DNA extraction kits. Microarrays with 9 common mutation loci of 4 deafness-associated genes in Chinese population were used. Nine hot mutations including GJB2 (35delG, 176del16, 235delC and 299delAT), GJB3 (538C> T), SLC26A4 (IVS 7-2A> G, 2168A> G), and mitochondrial DNA 12S rRNA (1555A> G, 1494C> T) were detected by PCR amplification and microarray hybridization. Mutations detected by microarray were verified by Sanger DNA sequencing.

RESULTSOf the 17 000 new-borns, 542 neonates had mutations of the 4 genes. Heterozygous mutations of GJB2, at 235delC, 299delAT, and 176del16 were identified in 254, 55, and 15 newborns, respectively. Two newborns had homozygous mutation of GJB2, 235delC. Heterozygous mutations at 538C> T of GJB3, 2168A> G and IVS 7-2A> G of SLC26A4 were found in 23, 17 and 128 newborns, respectively. For mutation analysis of mitochondrial DNA 12S rRNA, 1494C> T and 1555A> G were homogeneous mutations in 4 and 42 neonates, respectively. In addition, 6 complexity mutations were detected, which demonstrated that one newborn had heterozygous mutations at GJB2 235delC and SLC26A4, IVS7-2A> G, one had heterozygous mutation GJB2 235delC and 12S rRNA homogeneous mutation, 1555 A> G, one heterozygous mutations at GJB2, 299delAT, and GJB3, 538C> T, one at GJB2, 299delAT and 12S rRNA, 1555 A> G, two at GJB2, 299delAT, and SLC26A4, IVS7-2A> G. All mutations as above were confirmed by DNA sequencing.

CONCLUSIONThe total mutation carrier rate of the 4 deafness genes is 3.19% in healthy newborns at Chengdu. Mutations of GJB2 and SLAC26A4 are major ones (86.5% of total). The mutation rate of mitochondrial DNA 12S rRNA is 2.71‰, which may have deafness induced by aminoglycoside antibiotics. Newborn screening for mutation of genes related to hereditary deafness plays an important role in the early detection and proper management for neonatal deafness as well as genetic counseling for premarital, prenatal and postnatal diagnosis.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Connexin 26 ; Connexins ; genetics ; DNA Mutational Analysis ; DNA, Mitochondrial ; chemistry ; genetics ; Deafness ; diagnosis ; ethnology ; genetics ; Dried Blood Spot Testing ; Genetic Predisposition to Disease ; ethnology ; genetics ; Genetic Testing ; methods ; Humans ; Infant, Newborn ; Membrane Transport Proteins ; genetics ; Microarray Analysis ; methods ; Mutation ; Neonatal Screening ; methods ; RNA, Ribosomal ; genetics

Objective:To investigate the clinical features,differential diagnosis and treatment of intravascular NK/T cell lymphoma.Methods:The clinical data and diagnosis and treatment process of 2 patients with intravascular NK/T cell lymphoma admitted to Chongqing University Cancer Hospital were retrospectively analyzed, and related literatures were reviewed.Results:Both patients were initially presented with cutaneous symptoms. Patient 1 was diagnosed with intravascular NK/T cell lymphoma, and received 4 courses of programmed-death receptor 1 (PD-1) inhibitor toripalimab + P-Gemox (pegaspargase + gemcitabine + oxaliplatin) regimen, 1 course of PD-1 + ME (toripalimab + mitoxantrone + etoposide) regimen and then underwent autologous hematopoietic stem cell transplantation; patient 2 was diagnosed with intravascular NK/T cell lymphoma involving the nasal cavity, and received 4 courses of P-Gemox regimen, and then received autologous hematopoietic stem cell transplantation in the other hospital. Both patients achieved good therapeutic efficacy.Conclusions:Intravascular NK/T cell lymphoma is very rare, frequently involving the skin and central nervous system. Intravascular growth of tumor cells derived from NK cells is the key point of diagnosis and differential diagnosis. P-Gemox regimen and hematopoietic stem cell transplantation could bring better curative effect.