茎突综合征45例临床分析

目的 :提高茎突综合征的诊治水平。方法 :本组 45例中 ,双侧患者 18例 ,单侧患者 2 7例 (以X线 >3 0cm为标准 )。 45例均行手术治疗 ,经口内进路 2 1例 ,经颈外进路 2 4例。结果 :术后随访 0 5～ 2年 ,35例症状完全缓解 ,6例部分缓解 ,4例无效。治愈率为 77 8%。总有效率为 91 1%。结论 :茎突综合征临床无特异性。确诊需详问病史、触诊 ,结合影像学检查 ,并与其他疾病相鉴别。外科治疗为最有效方法。根据触诊结果选择手术进路。

茎突综合征134例分析

我科自1977年以来,收治茎突综合征134例,其中手术治疗128例,疗效显著,现报告于下: 临床资料 134例中,男72例,女62例,年龄20～29岁12例,39岁38例,49岁56例,59岁18例,69岁8例,70岁以上2例;单侧56例,双侧78例。病史最短者3天,最长者20余年,多数患者在数月或1～2年之间。主要症状:咽部异物感、梗塞感为主者46例,单侧咽痛、吞咽痛28例,下颌角及颈部阵发性痛18例,单侧耳深部痛伴耳鸣26例,腭弓舌根部6例,双耳深部痛伴耳鸣10例。本组病例有11例曾施行过扁桃体摘除术。

Novel mutations in the STK11 gene in Thai patients with Peutz-Jeghers syndrome

Peutz-Jeghers syndrome （PJS）, a rare autosomal dominant inherited disorder, is characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation. Patients with this syndrome have a predisposition to a variety of cancers in multiple organs. Mutations in the serine/threonine kinase 11 （STK11） gene have been identified as a major cause of PJS. Here we present the clinical and molecular findings of two unrelated Thai individuals with PJS. Mutation analysis by Polymerase Chain Reaction-sequencing of the entire coding region of STK11 revealed two potentially pathogenic mutations. One harbored a single nucleotide deletion （c.182delG） in exon 1 resulting in a frameshift leading to premature termination at codon 63 （p.Gly61AlafsX63）. The other carried an in-frame 9-base-pair （bp） deletion in exon 7, c.907_915del9 （p.Ile303_GIn305del）. Both deletions were de novo and have never been previously described. This study has expanded the genotypic spectrum of the STK11 gene.

Characterization of a Chinese KCNQ1 mutation （R259H） that shortens repolarization and causes short QT syndrome 2

Objectives To evaluate the association between a KCNQ 1 mutation, R259H, and short QT syndrome （SQTS） and to explore the elec- trophysiological mechanisms underlying their association. Methods We performed genetic screening of SQTS genes in 25 probands and their family members （63 patients）. We used direct sequencing to screen the exons and intron-exon boundaries of candidate genes that en- code ion channels which contribute to the repolarization of the ventricular action potential, including KCNQI, KCNH2, KCNE1, KCNE2, KCNJ2, CACNAlc, CACNB2b and CACNA2D1. In one of the 25 SQTS probands screened, we discovered a KCNQ1 mutation, R259H. We cloned R259H and transiently expressed it in HEK-293 cells; then, currents were recorded using whole cell patch clamp techniques. Results R259H-KCNQ 1 showed significantly increased current density, which was approximately 3-fold larger than that of wild type （WT） after a depolarizing pulse at 1 s. The steady state voltage dependence of the activation and inactivation did not show significant differences between the WT and R259H mutation （P 〉 0.05）, whereas the time constant of deactivation was markedly prolonged in the mutant compared with the WT in terms of the test potentials, which indicated that the deactivation of R259H was markedly slower than that of the WT. These results suggested that the R259H mutation can effectively increase the slowly activated delayed rectifier potassium current （Irs） in phase 3 of the cardiac action potential, which may be an infrequent cause of QT interval shortening. Conclusions R259H is a gain-of-function muta- tion of the KCNQ1 channel that is responsible for SQTS2. This is the first time that the R259H mutation was detected in Chinese people.

Deafness genes for nonsyndromic hearing loss and current studies in China

Objectives To review the identified deafness genes related to nonsyndromic hearing loss (NSHL) and summarize their expressions and functions in the cochlea and to introduce the current studies of molecular genetics on NSHL in China Methods The presented data are based on a review of the literature as well as the author's experience with NSHL and communications with other researchers in China over the past 3 years Results Currently, 23 deafness genes related to NSHL have been cloned and identified Some genes are associated with both NSHL and syndromic hearing loss (SHL), in both dominant and recessive deafness Deafness genes have a highly specific expression pattern in the inner ear Some functional categories are starting to emerge from a characterization of deafness genes There are interacting genes in the genetic background that influence the extent of hearing impairment The GJB3 gene, which is associated with high frequency hearing impairment, was cloned in a Chinese laboratory Mutations in some genes, such as GJB2 and mitochondrial 12S rRNA, have been screened in Chinese patients with NSHL Mapping new deafness gene loci as well as identifying new genes and their functions is an active area of study in China Conclusions It is challenging for us to continue identifying new deafness genes and analyze gene functions By identifying genes responsible for monogenic hearing impairment, more insight may be gained into the molecular process of hearing and the pathology of hearing loss

A novel large deletion mutation of FERMT1 gene in a Chinese patient with Kindler syndrome

Kindler syndrome （KS; OMIM 173650） is a rare autosomal recessive skin disorder, which results in symptoms including blistering, epidermal atrophy, increased risk of cancer, and poor wound healing. The majority of mutations of the disease-determining gene （FERMT1 gene） are single nucleotide substitutions, including missense mutations, nonsense mutations, etc. Large deletion mutations are seldom reported. To determine the mutation in the FERMT1 gene associated with a 7-year-old Chinese patient who presented clinical manifestation of KS, we performed direct sequencing of all the exons of FERMT1 gene. For the exons 2-6 without amplicons, we analyzed the copy numbers using quantitative real-time polymerase chain reaction （qRT-PCR） with specific primers. The deletion breakpoints were sublocalized and the range of deletion was confirmed by PCR and direct sequencing. In this study, we identified a new 17-kb deletion mutation spanning the introns 1-6 of FERMT1 gene in a Chinese patient with severe KS phenotypes. Her parents were carriers of the same mutation. Our study reported a newly identified large deletion mutation of FERMT1 gene involved in KS, which further enriched the mutation spectrum of the FERMT1 gene.

Clinical feature and waveform in infantile nystagmus syndrome in children with FRMD7 gene mutations

Infant nystagmus sydrome presents as involuntary eye movement disorder and can affect seriously ocular function. We performed a retrospective study of clinical data and FRMD7 genetic test results in 12 cases of infantile nystagmus syndrome to correlate waveform, stereopsis, and visual acuity. The patients(age 6.40±2.67 years) had FRMD7 mutations as follows: missense in eight cases, shear in two cases, frameshift in one case, and non-frameshift in one case. Horizontal jerk waveform was observed in six cases, versus horizontal pendulum in five cases and dual jerk in one case. The uncorrected visual acuity(24 eyes) was 0.21±0.12,compared with a corrected visual acuity(24 eyes) of 0.32±0.14. All patients had simultaneous perception, versus fusion function in 10 cases(83.33%) and stereoscopic vision in seven cases(58.33%) using the synoptophore. Eleven cases(91.67%) detected the stereo fly, compared with five cases(41.67%) for stereoscopic circles and seven cases(58.33%) for stereoscopic animals by Titmus test. Stereoscopic vision using the synoptophore did not correlate with the frequency, amplitude, or intensity of nystagmus or with corrected binocular visual acuity. The infantile nystagmus syndrome with FRMD7 mutations in our cases was caused primarily de novo and missense mutations. Visual acuity and binocular visual function were significant impaired, and the waveform was generally horizontal jerk. Also, an infrared videonystagmogram can record the frequency, amplitude, and intensity of nystagmus accurately.

Whole-exome sequencing identified compound heterozygous variants in MMKS in a Chinese pedigree with Bardet-Biedl syndrome

Bardet-Biedl syndrome(BBS) is a genetically heterogeneous disorder characterized by retinal dystrophy, polydactyly, obesity,developmental delay, and renal defects. At least 21 candidate BBS-associated genes(BBS1-19, NPHP1, and IFT172) have previously been identified, and all of them play important roles in ciliary function. Here, we collected a BBS pedigree with four members and performed whole-exome sequencing on the proband. The variants were analyzed and evaluated to confirm their pathogenicity. We found compound heterozygous variants(c.1192C>T, p.Q398* and c.1175C>T, p.T392M) in MKKS in both the siblings, and these were likely to be pathogenic variants. We also found a missense variant(c.2029G>C, p.E677Q) in NPHP1 and a missense variant(c.2470C>T, p.R824C) in BBS9 in the proband only, which are variants of uncertain significance. The compound heterozygous variants were probably responsible for the BBS phenotype in this Chinese pedigree and the missense mutations in NPHP1 and BBS9 might contribute to the mutation load.

Gene mutations and clinical phenotypes in Chinese children with Blau syndrome

The mutations of CARD15 gene and clinical features of Chinese patients with Blau syndrome were analyzed. We identified10 missense mutations, out of which five were new: R334 L, E383 D, R471 C, C495 R and D512 F. The rest of them, R334 W,R334Q, G481 D, M513 T and R587 C, have been reported previously. Among all the mutations, R334 W, R334 Q and C495 R had the highest frequency. Blau syndrome was found at early age after birth. It began with lepidic rash and symmetric polyarthritis and was phenotypically characterized by typical rash, arthritis, iridocyclitis and arteritis. Cardiac involvement was also found in Blau syndrome. In addition to nerve deafness, renal involvement, osteochondroma and central nervous system involvement were also found in our patients. Therefore, Chinese children with Blau syndrome have unique gene mutations and complicated clinical phenotypes. Pathologic examination and CARD15 mutation testing should be considered for diagnosis as early as possible for suspected patients.