Comparison between Bilateral and Unilateral Sudden Sensorineural Hearing Loss / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bilateral sudden sensorineural hearing loss (BSSHL) is rare and assumed to be a different clinical entity compared to unilateral SSHL (USSHL). This study examined the differences between the idiopathic BSSHL and USSHL.</p><p><b>METHODS</b>Forty-six sequential BSSHL patients (Se-BSSHL) and 68 simultaneous BSSHL (Si-BSSHL) were consecutively admitted between June 2008 and December 2015. Two sets of patients served as control groups: (1) USSHL patients with healthy contralateral ear and (2) USSHL patients with contralateral preexisting hearing loss (USSHLwCHL). We retrospectively analyzed differences among four cohorts using analysis of variance, Kruskal-Wallis test, Welch's t-test, and Chi-square test as appropriate before and after propensity score matching (PSM) based on age, gender, and body mass index (BMI).</p><p><b>RESULTS</b>The prevalence of idiopathic BSSHL was 8.6% (114/1329) among the total SSHL patients. In the total cohort, USSHL patients tended to be younger, female, and tended to have lower BMI, renal parameters, and total cholesterol in addition to higher high-density lipoprotein compared to the other three groups. Most routine blood indicators, some coagulation markers, and immunoglobulin M (H = 13.4, P = 0.004) were significantly different among the study groups. After PSM, the major significant differences were found in audiometric characteristics. Si-BSSHL and Se-BSSHL patients demonstrated similar hearing thresholds as USSHL but were significantly better than the USSHLwCHL patients across most frequencies before and after treatment (H = 30.0, P < 0.001 for initial hearing and H = 12.0, P = 0.007 for final hearing). Moreover, the BSSHL patients showed different hearing loss distribution patterns (more descending type, χ2 = 33.8, P = 0.001) with less hearing gain (H = 17.5, P < 0.001) compared to the USSHL patients.</p><p><b>CONCLUSIONS</b>Idiopathic BSSHL is a relatively rare subtype of SSHL with a higher rate of descending audiogram type and inferior hearing outcome rather than being classified as a completely different disease entity compared to USSHL.</p>

AMutation Causes Nonsyndromic Hearing Loss in a Chinese X-linked Recessive Family / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The molecular genetic research showed the association between X-linked hearing loss and mutations in POU3F4. This research aimed to identify a POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family.</p><p><b>METHODS</b>A series of clinical evaluations including medical history, otologic examinations, family history, audiologic testing, and a high-resolution computed tomography scan were performed for each patient. Bidirectional sequencing was carried out for all polymerase chain reaction products of the samples. Moreover, 834 controls with normal hearing were also tested.</p><p><b>RESULTS</b>The pedigree showed X-linkage recessive inheritance pattern, and pathogenic mutation (c.499C>T) was identified in the proband and his family member, which led to a premature termination prior to the entire POU domains. This mutation co-segregated with hearing loss in this family. No mutation of POU3F4 gene was found in 834 controls.</p><p><b>CONCLUSIONS</b>A nonsense mutation is identified in a family displaying the pedigree consistent with X-linked recessive pattern in POU3F4 gene. In addition, we may provide molecular diagnosis and genetic counseling for this family.</p>

Clinical Auditory Phenotypes Associated withGene Mutations in Familial Hypoparathyroidism-deafness-renal Dysplasia Syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Clinical Study on 136 Children with Sudden Sensorineural Hearing Loss / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The prevalence of sudden sensorineural hearing loss in children (CSSNHL) is consistently increasing. However, the pathology and prognosis of CSSNHL are still poorly understood. This retrospective study evaluated clinical characteristics and possible associated factors of CSSNHL.</p><p><b>METHODS</b>One hundred and thirty-six CSSNHL patients treated in Department of Otolaryngology-Head and Neck Surgery and Institute of Otolaryngology at Chinese PLA General Hospital between July 2008 and August 2015 were included in this study. These patients were analyzed for clinical characteristics, audiological characteristics, laboratory examinations, and prognostic factors.</p><p><b>RESULTS</b>Among the 136 patients (151 ears), 121 patients (121 ears, 80.1%) were diagnosed with unilaterally CSSNHL, and 15 patients (30 ears, 19.9%) with bilateral CSSNHL. The complete recovery rate of CSSNHL was 9.3%, and the overall recovery rate was 37.7%. We found that initial degree of hearing loss, onset of treatment, tinnitus, the ascending type audiogram, gender, side of hearing loss, the recorded auditory brainstem response (ABR), and distortion product otoacoustic emissions (DPOAEs) had prognostic significance. Age, ear fullness, and vertigo had no significant correlation with recovery. Furthermore, the relevant blood tests showed 30.8% of the children had abnormal white blood cell (WBC) counts, 22.1% had elevated homocysteine levels, 65.8% had high alkaline phosphatase (ALP), 33.8% had high IgE antibody levels, and 86.1% had positive cytomegalovirus (CMV) IgG antibodies.</p><p><b>CONCLUSIONS</b>CSSNHL commonly occurs unilaterally and results in severe hearing loss. Initial severe hearing loss and bilateral hearing loss are negative prognostic factors for hearing recovery, while positive prognostic factors include tinnitus, gender, the ascending type audiogram, early treatment, identifiable ABR waves, and DPOAEs. Age, vertigo, and ear fullness are not correlated with the recovery. Some serologic indicators, including the level of WBC, platelet, homocysteine, ALP, positive CMV IgG antibody, fibrinogen, and some immunologic indicators, are closely related to CSSNHL.</p>

Effect of High Quality Nursing on the Negative Emotion and Treatment Compliance of Patients with Leukemia / 昆明医科大学学报

Objective To observe the effect of high quality nursing care on the negative emotion and treatment compliance of patients with leukemia.Methods 116 patients with leukemia in our hospital from January 2010 to April 2014 were randomly divided into study group and control group,58 cases in each group.The control group was given routine nursing measures,and the research group was given high quality care measures based on the control group.Self rating Depression Scale (SDS) and self rating Anxiety Scale (SAS) was used to evaluate the adverse mood changes between the two groups before and after the intervention,and the treatment compliance,nursing satisfaction and the incidence of complications of the two groups were compared.Results After the intervention,SDS and SAS scores of the study group were significantly lower than those of the control group after the intervention,the difference was statistically significant (P＜0.05).The treatment compliance and satisfaction with nursing care of the study group were improved significantly than those of the control group (87.93％ vs 68.97％,96.55％ vs 81.03％),the difference was statistically significant (P＜0.05).The complication rate of the study group decreased significantly than that of the control group (15.52％ vs 31.03％),the difference was statistically significant (P＜0.05).Conclusion High quality nursing for patients with leukemia can significantly improve the psychological status of patients,improve the treatment compliance and nursing satisfaction,the incidence of complications decreased significantly.

Identification of Two Disease-causing Genes TJP2 and GJB2 in a Chinese Family with Unconditional Autosomal Dominant Nonsyndromic Hereditary Hearing Impairment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are more than 300 genetic loci that have been found to be related to hereditary hearing impairment (HHI), including 92 causative genes for nonsyndromic hearing loss, among which 34 genes are related to autosomal dominant nonsyndromic HHI (ADNSHHI). Traditional linkage analysis and candidate gene sequencing are not effective at detecting the ADNSHHI, especially for the unconditional families that may have more than one pathogenic cause. This study identified two disease-causing genes TJP2 and GJB2 in a Chinese family with unconditional ADNSHHI.</p><p><b>METHODS</b>To decipher the genetic code of a Chinese family (family 686) with ADNSHHI, different gene screening techniques have been performed, including linkage analysis, candidate genes screening, high-throughput sequencing and Sanger sequencing. These techniques were done on samples obtained from this family over a period of 10 years.</p><p><b>RESULTS</b>We identified a pathogenic missense mutation, c. 2081G>A (p.G694E), in TJP2, a gene that plays a crucial role in apoptosis and age-related hearing loss (ARHL). The mutation was co-segregated in this pedigree in all, but not in the two patients who presented with different phenotypes from the other affected family members. In one of the two patients, we confirmed that the compound heterozygosity for p.Y136* and p.G45E in the GJB2 gene may account for the phenotype shown in this patient.</p><p><b>CONCLUSIONS</b>We identified the co-occurrence of two genetic causes in family 686. The possible disease-causing missense mutation of TJP2 in family 686 presents an opportunity for further investigation into ARHL. It is necessary to combine various genes screening methods, especially for some unconventional cases.</p>

Clinical analysis of sudden sensorineural hearing loss in patients with different ages / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical materials of sudden sensorineural hearing loss (SSNHL) in different ages of patients, and explore their clinical characteristics and prognosis.</p><p><b>METHODS</b>A retrospective review was conducted by the clinical symptoms, predisposing factors and prognosis in SSNHL patients with different ages in the past two years (from 2008 to 2010). All patients were divided into three groups according to age, including Group 1 (0-18 years old), Group 2 (19-59 years old), and Group 3 (over 60 years old).</p><p><b>RESULTS</b>Part of patients (28.1%) had a clear history of virus infection in Group 1. Some patients (18.7%) had obvious history of emotional fluctuations or fatigue before the onset of SSNHL. Three groups of patients with "aural fullness" symptom accounted for 3.1%, 41.3% and 29.4% respectively. The proportions of patients with profound hearing loss in three groups were 62.5%, 40.0% and 33.3% respectively. Most patients improved hearing level during systemic internal medicine treatment. However, many patients (68.8%) in Group 1 showed poor therapeutic effect.</p><p><b>CONCLUSIONS</b>SSNHL in different age stages has different clinical features. We can improve the personalized treatment program to this disease through the classification and grading treatment.</p>

Influence of hepatocyte cell adhesion molecule on gene expression profile of human bladder transitional cell carcinoma cell line / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the changes of gene expression file in transitional cell carcinoma of bladder after hepatocyte cell adhesion molecule(hepaCAM) overexpression.</p><p><b>METHODS</b>Affymetrix Human Genome U133 Plus 2.0 Array was used to investigate the changes of gene expression profile between adenovirus-green fluorescent protein(GFP) -hepaCAM group and GFP group in transitional cell carcinoma of bladder EJ cells.Significant Analysis of Microarray(SAM) was used to screen the differentially expressed genes, DAVID software was used to conduct gene ontology analysis and wikiPathway analysis based on the differentially expressed genes. Reverse transcription-polymerase chain reaction and Western blot were applied to verify microarray data.</p><p><b>RESULTS</b>Compared with the GFP group, a total of 2469 genes were up-regulated or down-regulated by more than 2 times in the GFP-hepaCAM group. Among these genes, 1602 genes were up-regulated and 867 were down-regulated.Most of the differentially expressed genes were involved in the function of cell proliferation and cell cycle regulation. The mRNA expressions of nibrin, liver kinase B1, and cyclin D1 detected by reverse transcription-polymerase chain reaction in three different bladder cancer cell lines were consistent with the microarray data.The protein expressions of nibrin and liver kinase B1 in these three cell lines measured by Western blot were consistent with the mRNA expression.</p><p><b>CONCLUSIONS</b>HepaCAM can alter the gene expression profile of bladder cancer EJ cells. The well-known anti-tumor effect of hepaCAM may be mediated by regulating the gene expression via multiple pathways.</p>

Nonlinear finite element analysis of three implant- abutment interface designs / 国际口腔科学杂志·英文版

The objective of this study was to investigate the mechanical characteristics of implant-abutment interface design in a dental , using nonlinear finite element analysis (FEA) method. This finite element simulation study was applied on three commonly used commercial dental implant systems: model I, the reduced-diameter 3i implant system (West Palm Beach, FL, USA) with a hex and a 12-point double internal hexagonal connection; model II, the Semados implant system (Bego, Bremen, Germany) with combination of a conical (450 taper) and internal hexagonal connection; and model III, the Brinemark implant system (Nobel Biocare, Gothenburg,Sweden) with external hexagonal connection. In simulation, a force of 170 N with 45" oblique to the longitudinal axis of the implant was loaded to the top surface of the abutment. It has been found from the strength and stiffness analysis that the 3i implant system has the lowest maximum von Mises stress, principal stress and displacement while the Br Bnemark implant system has the highest. It was concluded from our preliminary study using nonlinear FEA that the reduced-diameter 3i implant system with a hex and a 12-point double internal hexagonal connection had a better stress distribution, and produced a smaller displacement than the other two implant systems.

Analysis of the hereditary etiology of 336 patients with non-syndromic sensorineural hearing loss from Ningxia Hui Autonomous Region of China / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the molecular genetic causes and their characteristics of deafness in Ningxia province, we established screening of three common hereditary deafness genes in 336 deaf and hard-of-hearing patients in this district.</p><p><b>METHODS</b>Peripheral blood samples were obtained from a total of 336 patients with non-syndromic sensorineural hearing loss in parts of special education schools in Ningxia province to extract genomic DNA. The mitochondrial DNA 12S rRNA m.1555A > G mutation was screened by PCR Alw26I digestion and sequence analysis PCR and direct sequencing were used to analyze the coding region of GJB2 and exons 8 and 19 of SLC26A4. Statistical analysis was performed by using SPSS 11.0 software. Frequencies of different GJB2 or SLC26A4 mutations were compared between Han and Hui people.</p><p><b>RESULTS</b>Among these 336 patients, seven cases (2.08%, 7/336) were found to carry mtDNA 12S rRNA m.1555A > G homozygous mutation, 45 cases (13.39%) were caused by GJB2 mutations and 28 cases (8.33%) had two mutated alleles (homozygote and compound heterozygote) of SLC26A4. In detail, 16.67% (56/336) patients carried GJB2 mutations including 11 single mutant carriers. The allele frequency of c.235delC and c.299_300delAT were 9.52% (64/672) and 2.68% (18/672), respectively, making up 81.19% (82/101) of all pathogenic mutated alleles for GJB2. The single mutant allele carriers of SLC26A4 is 32, and two types (c.919-2A > G and c.2168A > G) accounted for 95.29% (24/27) mutations, totally. We also found that statistically significant differences in c.919-2A > G and c.2168A > G frequencies between Han and Hui people (c.919-2A > G, χ(2) = 8.229, P = 0.004; c.2168A > G, χ(2) = 5.277, P = 0.022). However, there was no statistically significant difference in GJB2 mutation between Han and Hui people.</p><p><b>CONCLUSIONS</b>GJB2 mutation was a primary cause for non-syndromic sensorineural hearing loss in Ningxia province, and c.235delC was the most common mutant forms of GJB2. c.919-2A > G and c.2168A > G were common mutant forms of SLC26A4, their frequencies were also statistically significant differences between Han and Hui people.</p>

Analysis of improper pattern of Mandarin monosyllable recognition test among the patients with auditory neuropathy / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To analyze the improper pattern in mandarin monosyllable recognition test among the patients with Auditory Neuropathy (AN) in order to work out the common characteristics in speech recognition which might be suitable for diagnosis of AN.</p><p><b>METHODS</b>Sixteen AN patients (32 ears) were studied and 22 patients (32 ears) with sensorineural hearing loss (SNHL) were set for control. In accordance with audiogram pattern, all subjects were then divided into the up-type hearing (15 ears) and non up-type hearing (17 ears) groups. All 64 ears were tested in high intensity by mandarin monosyllable test material which we have developed before. Monosyllable performance scores from testing ears and improper patterns were recorded respectively. Eight improper patterns were then defined as follows: consonant only, vowel only, tone only, consonant and vowel, consonant and tone, vowel and tone, all phonemes and no response.</p><p><b>RESULTS</b>The score of patients with AN was lower than those patients with SNHL in monosyllable recognition test (P < 0.001). No significant difference was found between subgroup of up-type hearing loss and SNHL group in percentage correct scores of monosyllables, consonants, vowels, and tones statistically (P > 0.05), but significant lower score was found in subgroup of non up-type hearing loss compared with SNHL group in these 4 percentage scores concerned (P < 0.001). Chi square test presented a significant difference in improper pattern proportion between AN and SNHL groups (P < 0.001), which could be related to more proportional tone recognition in the former's incorrect items. Improper pattern proportions between two AN subgroups presented a significant difference statistically (P < 0.001), which could be related to a larger proportional recognition of tones and vowels in subgroup of up-type hearing loss compared with subgroup of non up-type hearing loss.</p><p><b>CONCLUSIONS</b>A poor performance might be a major clinical feature identified AN from SNHL in mandarin tone recognition. There are significant differences between AN patients with up-type hearing loss and patients with non up-type hearing loss in performance of monosyllable recognition and improper pattern proportion of tones and vowels. A psychophysical testing may be a key potential in diagnosis of AN in further clinical application.</p>

Audiological and genetic studies on 130 infants with hearing loss / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the genetic etiologies in the 0- 3-years-old infants with hearing loss and to analyze the interaction between genetics and environmental factors.</p><p><b>METHODS</b>Total of 130 infants were performed detailed audiological evaluation as well as the detection of the popular deafness gene mutations in GJB2 gene, SLC26A4 and mtDNA12SrRNA. Of them, 84 cases were performed the computer tomography or magnetic resonance imaging examinations.</p><p><b>RESULTS</b>Of the 130 cases, 54 infants were diagnosed as large vestibular aqueduct syndrome, while seven of 130 were as auditory neuropathy and the others were diagnosed as sensorineural hearing loss. Considering of the risks of etiologies for hearing loss, 85 of them had the experiences of the high risk factors at birth (65.4%, 85/130), while 23 of them had the exposure of aminoglycoside antibiotics, and 13 had the family history background as well as two cases were from the consanguineous families. In the causative genes screening, 42 infants were caused by the mutations of SLC26A4 gene (32.3%), but 14 infants found the mutations in GJB2 gene (4.6%), and no infants carried the mutation in mtDNA 12SrRNA 1555G and 1494T points in our studies.</p><p><b>CONCLUSIONS</b>In our studies, about 36.9% infants hearing loss cases can be found the mutations in SLC26A4 and GJB2 genes. It is essential to put the idea into the hearing evaluation combined with genetic testing for the diagnoses of hearing loss. It is also helpful for exploring the etiologies of hearing loss and performing the target genetic consulting for decreasing the prevalence of deafness in the future.</p>

Audiological characteristics of young children with otitis media with effusion / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To characterize the audiological features in the infants with otitis media with effusion (OME) and to investigate the utility of variety of objective audiometry methods in diagnosis and intervention on OME.</p><p><b>METHODS</b>Fifty six infants (40 males and 16 females) were investigated, who were referred to our clinic at the General Hospital of Chinese People's Liberation Army by the other hospitals from December 2004 to June 2007 when the infants were diagnosed or highly suspected of OME. The ages at the initial diagnosis ranged from 42 days to three years, with an average of five months. The infants, after receiving the conventional otolaryngological exams, were subjected to the tests of auditory brainstem response (ABR), otoacoustic emission (OAE), tympanometry (226 Hz and 1000 Hz) and behaviors audiometry.</p><p><b>RESULTS</b>Among 56 affected infants, 87 ears were diagnosed with OME, of which 31 infants were affected bilateral and 25 with monaural. For the 49 infants who received hearing screening at birth, 36 infants were referred at the initial screening. For the 52 infants who received repeated screening, all subjects were referred. Six infants without receiving hearing screening came to clinic when their parents observed their kids' hearing impairment. Among the 52 cases (104 ears) who received tympanometry test, 20 subjects (28 ears) showed B or C type tympanometry curve. Thirty-nine cases (78 ears) were given tympanometry test at 1000 Hz, of which 38 cases (55 ears) showed abnormal hearing. Among 56 infants (112 ears) with ABR test, 49 subjects (74 ears) exhibited prolonged ABR type I curve. All 56 infants (112 ears) received OAE test, of which 55 subjects (81 ears) were referred. Four infants (8 ears) accepted the behavior test and all of them showed A-B Gap.</p><p><b>CONCLUSIONS</b>The combined tympanometry test at both 226 Hz and 1000 Hz, ABR latency or threshold test, infant's behavior test and OAE, used jointly, enable characterizing better OME in infants, thus helping early diagnosis of this hearing disorder.</p>

Correlation between phonetically balanced maximum and pure tone auditory threshold among 106 auditory neuropathy patients / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To estimate correlation between phonetically balanced maximum (PB max) and pure tone auditory threshold in auditory neuropathy (AN) patients.</p><p><b>METHODS</b>One hundred and six AN patients were identified using multiple criteria including PB max, a metric for speech recognition, pure tone auditory threshold, acoustic emission test, distortion products otoacoustic emission (DPOAE) and auditory brainstem response (ABR). SPSS statistical software was used to estimate the Pearson's correlation between PB max and pure tone auditory threshold and to test whether pure tone auditory threshold, or auditory configuration had a significant impact on PB max.</p><p><b>RESULTS</b>Even the patients had the same or similar values for pure tone auditory threshold or auditory configuration, varied values of PB max were found in two hundreds and twelve ears for 106 patients. Analysis of the data for 106 patients revealed a negative correlation (r = -0. 602, P <0. 01) between PB max and pure tone auditory threshold, i. e. hearing loss at a mild relates to a lower PB max. By using analysis of variance (ANOVA) method, it was found that both pure tone auditory threshold and auditory configuration had a significant (P <0.01) impact on the patients' PB max.</p><p><b>CONCLUSIONS</b>This analysis implicated the promise and potential of pure tone auditory threshold and auditory configuration for predicting PB max of the AN patients, and improving the diagnosis of AN.</p>

Mitochondrial DNA A1555G mutation analysis in 802 nonsyndromic hearing impairment patients / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of the mitochondrial DNA (mtDNA) A1555G mutation in nonsyndromic hearing impairment (NSHI) patients from Gansu province.</p><p><b>METHODS</b>Subjects included 802 students selected from five Deaf-Mute Schools in Gansu. DNA was extracted from peripheral blood of all patients. The mitochondrial DNA target fragments were amplified by polymerase chain reaction (PCR). The Mutations were detected by AIw26I digestion and sequence analysis.</p><p><b>RESULTS</b>The homoplasmic A1555G mutation was found in 67 individuals from 802 patients (8.4%). Fifteen of these 67 patients had family histories.</p><p><b>CONCLUSIONS</b>The mtDNA A1555G mutation had a higher incidence in Gansu population with nonsyndromic hearing impairment than other studies. The data not only gaven more evidences that the prevalence of mtDNA A1555G mutation in china was higher than that in Europe and America, but also gaven valuable information for gene diagnosis, genetic counseling and would improve the safety of aminoglycoside antibiotic therapy.</p>

Studies of the strategy for newborn gene screening / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To discuss and analyze the feasibility and strategy for perform the newborn gene screening in the process of newborn hearing screening in order to supply the defects or limitation in the hearing screening.</p><p><b>METHODS</b>Four hundreds and sixty newborn babies from December 2006 to April 2007 accepted the simultaneous hearing and gene screening. Otoacoustic emission (OAE) was used for the first step hearing screening and OAE combined with auto auditory brainstem response (AABR) detection for the second step screening. Newborn genetic disease screening cards were used for collecting the blood spot from the umbilical cord within the moment of newborn. The cards could be directly performed the polymerase chain reaction (PCR) for screening the mitochondrial 12SrRNA 1555G and GJB2 as well as SLC26A4 genes mutations. The restriction enzyme Alw26I was used to recognize the point mutation of 12SrRNA A1555G. The samples with the possible 12SrRNA A1555G mutation were then sequenced to verify. The PCR products from the GJB2 coding region and SLC26A4 IVS7-2A > G hot spot region were sequenced directly. The software of DNAStar was used to analysis the sequence.</p><p><b>RESULTS</b>The first step of hearing screening of 460 newborn babies showed " refer" on the left ear of nine babies and on the right ear of three babies. Seven showed "refer" on bilateral with the the total of babies 19. After 42 days, they accepted the second step for hearing screening. 16 of the 19 were showed "pass" with OAE and AABR. One baby showed "pass" on the left ear, "refer" on the right ear with the OAE detection but bilateral "pass" with AABR. Two babies failed to accept the re-examination. The newborn gene screening showed five of the 460 babies had the positive response on the A1555G restriction enzyme assay. Of the five babies, one was proved to be the 12SrRNA A1555G mutation and three were the C1556T mutations and one sequence was normal. For the SLC26A4 gene screening, five were the heterozygote of IVS7-2A > G mutation were found and one was carrier the polymorphism of IVS7-18T > G and another was IVS6-62_63insGT heterozygote carrier. For the GJB2 gene screening, eight were 235delC heterozygote carriers, four were G109A heterozygote carriers. All the gene screening found 23 newborn babies of the 460 harbored the changes in the three genes. Of those, one was the 12SrRNA A1555G. pathogenic mutation and 13 were pathogenic heterozygote carriers, nine were the polymorphisms. It was worth to pay more attentions that A1555G mutation was found in the baby whose hearing screening was "pass" in the hearing screening as well as the 13 heterozygote carrier for GJB2 and SLC26A4 gene.</p><p><b>CONCLUSIONS</b>It might be one of the powerful strategy for adding the concept of newborn gene screening into the hearing screening for the purpose of early diagnosis and discovery the prelingual or late-onset or the high risk as well as the pathogenic carriers. On the basis of the research progress, it was necessary to develop the national newborn gene screening into the process of newborn hearing screening.</p>

Gene mapping for autosomal dominant nonsyndromic hearing loss DFNA11 / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To map the gene locus in a Chinese pedigree with autosomal dominant nonsyndromic hearing loss.</p><p><b>METHODS</b>A genome wide screening was performed with 394 microsatellite markers distributed with an average spacing of 10 cM (ABI Prism Linkage Mapping Set 2, Applied Biosystems, Foster City, CA, U.S.A.).</p><p><b>RESULTS</b>Affected family members showed a bilateral, symmetrical, progressive neurosensory deafness. Significant linkage was found to marker D1 S937 (maximum two point LOD score of 5. 71 at theta = 0.05) on chromosome 11q. The position of the novel deafness locus, DFNA11, was delimited by analysis of the recombinant haplotypes (D11S165-D11S1874). This analysis placed DFNA11 between the proximal marker D11S1314 and the distal marker D11S898, which define a critical interval of 25.34 cM.</p><p><b>CONCLUSIONS</b>Mapping of the DFNA11 locus further confirms the great genetic heterogeneity underlying the autosomal dominant forms of hereditary deafness. Reports of more families with hearing impairment linked to this locus should contribute to the identification of the responsible gene, providing insights into the auditory function and the molecular pathophysiology of age related hearing loss.</p>

Prenatal diagnosis for hereditary deaf families assisted by genetic testing / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To provide prenatal diagnosis for deaf families, which the first child was confirmed to be hereditary deafness caused by gap junction beta-2 (GJB2) or SLC26A4 (PDS) mutation, to avoid another deaf birth in these families.</p><p><b>METHODS</b>Eight deaf families joined in this study. Each family had one child with severe to profound hearing loss while parents had normal hearing except a deaf father from family 8; mothers had been pregnant for 6-28 weeks. Genetic testing of GJB2, SLC26A4 and mitochondrial DNA (mtDNA) A1555G mutation were firstly performed in probands and their parents whose DNA was extracted from peripheral blood, and then prenatal testing was carried out in the fetus whose DNA was extracted from different fetus materials depending on the time of gestation.</p><p><b>RESULTS</b>The probands from family 1-4 were found to carry homozygous or compound GJB2 mutations while their parents carried corresponding heterozygous GJB2 mutations. The probands from family 5-8 and the deaf father from family 8 were found to carry compound SLC26A4 mutations while their parents and the mother from family 8 carried a single SLC26A4 mutation. Prenatal testing showed that the fetuses from family 1, 5, 8 only carried the paternal mutation and the fetuses from family 2, 3, 6 didn't carry any GJB2 or SLC26A4 mutations. The new born babies from these six families all had normal hearing revealed by new born hearing screening. However, the fetuses from family 4,7 carried the same mutations with probands in each family. The parents from family 4, 7 decide to terminate pregnancy.</p><p><b>CONCLUSION</b>Prenatal diagnosis assisted by genetic testing can provide efficient information about hearing condition of their offsprings.</p>

Clinical classification and relationship with conductive deafness of congenital middle ear malformations / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical classification and relationship with conductive deafness of congenital middle ear malformations.</p><p><b>METHODS</b>From 1995 to 2004, 64 patients (82 ears) with single congenital middle ear malformations were operated in the ENT department of the General Hospital of Chinese People's Liberation Army. According to the histology and embryology of middle ear and the findings of surgical exploration, the clinical classification was performed. Statistical analysis was used to judge the differences of hearing loss in different type of congenital middle ear malformations.</p><p><b>RESULTS</b>According to the embryologic development of the structures in middle ear, congenital middle ear malformations were classified 4 types. Type A: congenital ossicular chain anomalies; type B: congenital fusion of stapes; type C: congenital hypoplasia or atresia of oval/round widows. Hearing loss of three types on language frequency have no obvious difference (P = 0.1617), but there were statistical difference on high frequency ( > 2 kHz) between type A with type B and type C (P <0.05). Furthermore, descension of bone conduction and mixed deafness were familiar in type B and C.</p><p><b>CONCLUSIONS</b>According to embryologic development, it was rational that congenital middle ear malformations were classed 3 types mentioned above. Hearing loss due to middle ear malformations could be distinguished by descension of bone conduction and air conduction on high frequency ( >2 kHz).</p>

Clinical and Electroencephalography Characteristics of Benign Epilepsy with Centro-Temporal Spikes in Children / 实用儿科临床杂志

Objective To summarize the clinical and electroencephalography(EEG) characteristics of benign epilepsy with centro-temporal spikes (BECTS) in children.Methods The clinical manifestations,EEG findings,response to drug treatment and prognosis of 35 children with BECTS from Jul.2003 to Dec.2008 in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively.Results In the 35 cases,the age of onset was 2.5 to 14.0 years old,and the peak age of onset was 6-10 years old(62.9%).Twenty-two cases mainly presented partial seizures:hemifacial convulsions,sialorrhea,sounds,limb tonic-clonic seizures,and secondary generalized seizures.Thirteen cases were only describled generalized tonic-clonic seizures.Seizures were closely related to sleep and almost occurred shortly after falling asleep or before waking up.There were 26 cases who displayed convulsion during sleeping,including noon break.The EEG features showed numerous or single spikes on one side or both sides in the central and temporal areas under the background of normal activity in interictal period.The release frequency of abnormal wave was significantly increased after falling asleep,so the EEG monitoring during sleep could improve the positive rate of BECTS.Monotherapy with low-dose anti-epileptic drug could obtain good efficacy.Twenty-five cases stopped seizures within 3 months after therapy.Thirty-three cases hadn't get seizure since drug therapy at the age of 16 years old.So far,12 cases had been stopped medicine.Conclusions BECTS mostly begins at school-aged children,which displays partial seizures or secondary generalized seizures.The seizures are closely related to sleep.EEG monitoring during sleep which shows numerous or single spikes on the centrotemporal area has crucial diagnostic value to BECTS.There is a positive response to monotherapy with low-dose anti-epileptic drug and generally the prognosis is good.