Genetic screening of newborns for deafness over 11 years in Beijing, China: More infants could benefit from an expanded program.

Genetic screening of newborns for deafness plays an important role in elucidating the etiology of deafness, diagnosing it early, and intervening in it. Genetic screening of newborns has been conducted for 11 years in Beijing. It started with a chip to screen for 9 variants of 4 genes in 2012; the chip screened for 15 variants of those genes in 2018, and it now screens for 23 variants of those genes. In the current study, a comparative analysis of three screening protocols and follow-up for infants with pathogenic variants was performed. The rates of detection and hearing test results of infants with pathogenic variants were analyzed. Subjects were 493,821 infants born at 122 maternal and child care centers in Beijing from April 2012 to August 2023. Positivity increased from 4.599% for the chip to screen for 9 variants to 4.971% for the chip to screen for 15 variants, and further to 11.489% for the chip to screen for 23 variants. The carrier frequency of the GJB2 gene increased from 2.489% for the chip to screen for 9 variants and 2.422% for the chip to screen for 15 variants to 9.055% for the chip to screen for 23 variants. The carrier frequency of the SLC26A4 gene increased from 1.621% for the chip to screen for 9 variants to 2.015% for the chip to screen for 15 variants and then to 2.151% for the chip to screen for 23 variants. According to the chip to screen for 9 variants and the chip to screen for 15 variants, the most frequent mutant allele was c.235delC. According to the chip to screen for 23 variants, the most frequent mutant allele was c.109G>A. The chip to screen for 15 variants was used to screen 66.67% (14/21) of newborns with biallelic variants in the SLC26A4 gene for newly added mutations. The chip to screen for 23 variants was used to screen 92.98% (53/57) of newborns with biallelic variants in the GJB2 gene (52 cases were biallelic c.109G>A) and 25% (1/4) of newborns with biallelic variants in the SLC26A4 gene for newly added mutations. Among the infants with pathogenic variants (biallelic variants in GJB2 or SLC26A4), 20.66% (25/121) currently have normal hearing. In addition, 34.62% (9/26) of newborns who passed the hearing screening were diagnosed with hearing loss. Findings indicate that a growing number of newborns have benefited, and especially in the early identification of potential late-onset hearing loss, as the number of screening sites has increased. Conducting long-term audiological monitoring for biallelic variants in individuals with normal hearing is of paramount significance.

[The use of visual feedback in the treatment of a deaf young man with puberphonia]. / Primenenie vizual'noi obratnoi svyazi pri lechenii glukhogo yunoshi s puberfoniei.

A case of successful correction of the pitch frequency using the computer program Circ FFT is described.

Duration of cochlear implant use in children with prelingual single-sided deafness is a predictor of word perception in the CI ear.

As part of a longitudinal study regarding the benefit of early cochlear implantation for children with single-sided deafness, the current work explored the children's daily device use, potential barriers to full-time device use, and the children's ability to understand speech with the cochlear implant (CI). Data were collected from 20 children with prelingual SSD who received a CI before the age of 2.5 years, from the initial activation of the sound processor until the children were 4.8 to 11.0 years old. Daily device use was extracted from the CI's data logging, while word perception in quiet was assessed using direct audio input to the children's sound processor. The children's caregivers completed a questionnaire about habits, motivations, and barriers to device use. The children with SSD and a CI used their device on average 8.3 h per day, corresponding to 63 % of their time spent awake. All children except one could understand speech through the CI, with an average score of 59 % on a closed-set test and 73 % on an open-set test. More device use was associated with higher speech perception scores. Parents were happy with their decision to pursue a CI for their child. Certain habits, like taking off the sound processor during illness, were associated with lower device use. Providing timely counselling to the children's parents, focused on SSD-specific challenges, may be helpful to improve daily device use in these children.

Cochlear implantation in pediatrics: Impact of newborn hearing screening on intervention time.

OBJECTIVES: The newborn hearing screening (NHS) program was globally established for early hearing loss (HL) identification and intervention. Early intervention is essential to minimize or prevent the negative consequences of HL. In Saudi Arabia, the NHS was officially implemented in 2016. Currently, its impact on the timing of cochlear implantations (CIs) in Saudi Arabia remains unclear, and information on potential hospital-related delays affecting early implantation is lacking. Thus, this study aimed to evaluate the effect of implementing the NHS on age at CI in children with prelingual deafness in a CI center in Saudi Arabia, and to evaluate the hospital timing in the CI process. METHODS: All pediatric CI users who presented for the first time to the CI committee (CIC) at a tertiary center and received their implants between 2015 and 2022 were enrolled in this study. Date of birth (DOB), date of presentation to the CI committee (DOCIC), and date of CI surgery (DOCIS) were retrospectively reviewed. RESULTS: In total, 304 CI children were included in the analysis. Approximately 55 % of the children (n = 167) were screened for HL through the NHS, whereas 45 % of the children (n = 137) were born before the launch of the NHS. Both age at the presentation to the CIC (i.e. difference between DOCIC and DOB) and age at implantation (i.e. difference between DOCIS and DOB) were significantly earlier in children who were screened for HL through the NHS than those who were not screened (P < 0.0001). The time difference between the DOCIC and DOCIS was not significantly different between the screened and unscreened children (P > 0.05). CONCLUSION: The implementation of the NHS in the tertiary center has a significant positive effect on age at presentation to the CIC and age at implantation, but not on the actual CI surgery. Further research is needed to reduce the hospital delays before the actual surgery in order to increase the likelihood of children receiving implantation early in their life.

[Mutation spectrum analysis of 23-site chip neonatal deafness genetic screening].

Objective:To analyze the mutation spectrum of 23-site chip newborn deafness genetic screening in Beijing, and to provide basis for genetic counseling and clinical diagnosis and treatment. Methods:The study included 21 006 babies born in Beijing from December 2022 to June 2023. All subjects underwent newborn deafness genetic screening in Beijing Tongren Hospital, covering 23 variants in 4 genes, the GJB2 gene（c.35delG, c.176_191del16, c.235delC, c.299_300delAT, c.109G>A, c.257C>G, c.512insAACG, c.427C>T, c.35insG）, SLC26A4 gene（c.919-2A>G, c.2168A>G, c.1174A>T, c.1226G>A, c.1229C>T, c.1975G>C, c.2027T>A, c.589G>A, c.1707+5G>A, c.917insG, c.281C>T）, Mt12SrRNA（m.1555A>G, m.1494C>T） and GJB3 gene（c.538C>T）. The mutation detection rate and allele frequency were analyzed. Results:The overall mutation detection rate was 11.516%（2 419/21 006）, with the GJB2 gene being the most frequently involved at 9.097%（1 911/21 006）, followed by the SLC26A4 gene at 2.123%（446/21 006）, the GJB3 gene at 0.362%（76/21 006） and Mt12SrRNA at 0.176%（37/21 006）. Among the GJB2 genes, c.109G>A and c.235delC mutation detection rates were the highest, with 6.579%（1 382/21 006） and 1.795%（377/21 006）, respectively. Of the SLC26A4 genes, c.919-2A>G and c.2168A>G had the highest mutation rates of 1.423%（299/21 006） and 0.233%（49/21 106）, respectively. Regarding the allele frequency, GJB2 c.109G>A was the most common variant with an allele frequency of 3.359%（1 411/42 012）, followed by the GJB2 c.235delC at 0.897%（377/42 012） and the SLC26A4 c.919-2A>G at 0.719%（302/42 012）. Conclusion:23-site chip newborn deafness genetic screening in Beijing showed that GJB2 c.109G>A mutation detection rate and allele frequency were the highest. This study has enriched the epidemiological data of 23-site chip genetic screening mutation profiles for neonatal deafness, which can provide evidence for clinical practice.

Targeted Linked-Read Sequencing for Direct Haplotype Phasing of Parental GJB2/SLC26A4 Alleles: A Universal and Dependable Noninvasive Prenatal Diagnosis Method Applied to Autosomal Recessive Nonsyndromic Hearing Loss in At-Risk Families.

Noninvasive prenatal diagnosis (NIPD) for autosomal recessive nonsyndromic hearing loss (ARNSHL) has been rarely reported until recent years. Additionally, the existing method can not be used for challenging genome loci (eg, copy number variations, deletions, inversions, or gene recombinants) or on families without proband genotype. This study assessed the performance of relative haplotype dosage analysis (RHDO)-based NIPD for identifying fetal genotyping in pregnancies at risk of ARNSHL. Fifty couples carrying pathogenic variants associated with ARNSHL in either GJB2 or SLC26A4 were recruited. The RHDO-based targeted linked-read sequencing combined with whole gene coverage probes was used to genotype the fetal cell-free DNA of 49 families who met the quality control standard. Fetal amniocyte samples were genotyped using invasive prenatal diagnosis (IPD) to assess the performance of NIPD. The NIPD results showed 100% (49/49) concordance with those obtained through IPD. Two families with copy number variation and recombination were also successfully identified. Sufficient specific informative single-nucleotide polymorphisms for haplotyping, as well as the fetal cell-free DNA concentration and sequencing depth, are prerequisites for RHDO-based NIPD. This method has the merits of covering the entire genes of GJB2 and SLC26A4, qualifying for copy number variation and recombination analysis with remarkable sensitivity and specificity. Therefore, it has clinical potential as an alternative to traditional IPD for ARNSHL.

Hearing Loss: Genetic Testing, Current Advances and the Situation in Latin America.

Congenital hearing loss is the most common birth defect, estimated to affect 2-3 in every 1000 births, with ~50-60% of those related to genetic causes. Technological advances enabled the identification of hundreds of genes related to hearing loss (HL), with important implications for patients, their families, and the community. Despite these advances, in Latin America, the population with hearing loss remains underdiagnosed, with most studies focusing on a single locus encompassing the GJB2/GJB6 genes. Here we discuss how current and emerging genetic knowledge has the potential to alter the approach to diagnosis and management of hearing loss, which is the current situation in Latin America, and the barriers that still need to be overcome.

Community Health Navigators for Cancer Screening Among Deaf, Deafblind, and Hard of Hearing Adults Who Use American Sign Language.

Deaf, deafblind, and hard of hearing (DDBHH) individuals experience barriers to accessing cancer screening, including ineffective patient-physician communication when discussing screening recommendations. For other underserved communities, culturally and linguistically aligned community health navigators (CHNs) have been shown to improve cancer screening and care. A needs assessment study was conducted to identify barriers and gather recommendations for CHN training resources. A community-based participatory needs assessment was conducted from May 2022 to June 2022 using three focus groups. Eight were cancer survivors, six advocates/navigators, and three clinicians. All questions were semi-structured and covered screening barriers, observations or personal experiences, perceived usefulness of having a CHN to promote cancer screening adherence, and training resources that may be useful to American Sign Language (ASL)-proficient CHNs, who are also culturally and linguistically aligned. Out of 20 focus group participants, seven self-identified as persons of color. Data highlighted systemic, attitudinal, communication, and personal-level barriers as recurrent themes. The most frequently cited barrier was access to training that supports the role and competencies of CHNs, followed by cultural considerations, access to cancer guidelines in ASL, dialect diversity in sign language, and the health system itself. Unaddressed barriers can contribute to health disparities, such as lower preventive cancer screening rates amongst DDBHH individuals. The next step is to translate recommendations into actionable tasks for DDBHH CHN training programs. As a result, CHNs will be well-equipped to help DDBHH individuals navigate and overcome their unique barriers to cancer screening and healthcare access.

Analysis of deafness susceptibility gene of neonates in northern Guangdong, China.

This study aimed to explore the molecular epidemiology characteristics of deafness susceptibility genes in neonates in northern Guangdong and provide a scientific basis for deafness prevention and control. A total of 10,183 neonates were recruited between January 2018 and December 2022 at Yuebei People's Hospital. Among these, a PCR hybridization screening group of 8276 neonates was tested for four deafness genes: GJB2, SLC26A4, mtDNA, and GJB3 by PCR hybridization. Another group used next-generation sequencing (NGS) to detect genetic susceptibility genes in 1907 neonates. In PCR hybridization screening group, 346 (4.18%) of 8276 neonates were found to be carriers of the deafness gene. Among these, 182 (2.2%) had GJB2 variants, 114 (1.38%) had SLC26A4 variants, 35 (0.42%) had mtDNA variants, and 15 (0.18%) had GJB3 variants. In NGS Screening Group, 195 out of 1907 neonates were found to be carriers of the deafness gene, with a positive rate of 10.22%. Among these, 137 (7.18%) had GJB2 variants, 41 (2.15%) had SLC26A4 variants, 11 (0.58%) had mtDNA variants, and 6 (0.31%) had GJB3 variants. The prevalence of deafness gene variants was high in Northern Guangdong Province. The most common gene for deafness was GJB2, followed by SLC26A4 and mtDNA. GJB3 variants are rare. Compared with PCR hybridization method, NGS technology can expand the screening scope and greatly improve the detection rate of deafness genes. The c.109G>A of GJB2 was found to occur at a high frequency, which should be considered. Therefore, it is important to conduct neonatal deafness gene screening to prevent and control hereditary deafness.

A novel method for detecting nine hotspot mutations of deafness genes in one tube.

Deafness is a common sensory disorder. In China, approximately 70% of hereditary deafness originates from four common deafness-causing genes: GJB2, SLC26A4, GJB3, and MT-RNR1. A single-tube rapid detection method based on 2D-PCR technology was established for nine mutation sites in the aforementioned genes, and Sanger sequencing was used to verify its reliability and accuracy. The frequency of hotspot mutations in deafness genes was analysed in 116 deaf students. 2D-PCR identified 27 genotypes of nine loci according to the melting curve of the FAM, HEX, and Alexa568 fluorescence channels. Of the 116 deaf patients, 12.9% (15/116) carried SLC26A4 mutations, including c.919-2A > G and c.2168A > G (allele frequencies, 7.3% and 2.2%, respectively). The positivity rate (29.3%; 34/116) was highest for GJB2 (allele frequency, 15.9% for c.235delC, 6.0% for c.299_300delAT, and 2.6% for c.176-191del16). Sanger sequencing confirmed the consistency of results between the detection methods based on 2D-PCR and DNA sequencing. Common pathogenic mutations in patients with non-syndromic deafness in Changzhou were concentrated in GJB2 (c.235delC, c.299_300delAT, and c.176-191del16) and SLC26A4 (c.919-2A > G and c.2168 A > G). 2D-PCR is an effective method for accurately and rapidly identifying deafness-related genotypes using a single-tube reaction, and is superior to DNA sequencing, which has a high cost and long cycle.

Analysis of selective screening for congenital cytomegalovirus in a secondary hospital: Problems and solutions.

Universal hearing screening offers unique possibilities for detection of congenital deafness as a consequence of congenital cytomegalovirus (CMVc) infection, so its selective study in the case of a failed test could be a non-negligible screening opportunity while other guidelines covering the possibility of universal screening are adopted. The aim of this study is to analyse the possibility of selective screening for CMVc after an altered hearing test in a regional hospital. During the period studied, the results obtained were unsatisfactory, especially in children born outside the hospital of residence, showing an excessive delay in hearing screening in many cases and in the few cases where CMVc screening could be performed, only 30% had the test ordered in a timely manner. The reasons for this are varied and the solution is to include selective screening for CMVc in the hearing screening programme. This implies shortening the timing of the hearing screening protocol to allow CMVc testing in saliva or urine (preferably) before 21 days of age and providing screening programmes with the necessary staff and time to perform it properly.

Mutation analysis of GJB2, SLC26A4, GJB3 and mtDNA12SrRNA genes in 251 non-syndromic hearing loss patients in Fujian, China.

OBJECTIVES: The molecular etiology of non-syndromic hearing loss (NSHL) in Southeastern China (Fujian) has not been precisely identified. our study selected patients with NSHL and analyzed their causative genes, which helped to improve the accuracy of the diagnosis of hereditary hearing loss (HHL) and its treatment. METHODS: 251 unrelated patients who attended the otolaryngology clinic of Fujian Maternal and Child Health Hospital with hearing loss were enrolled to our study. All patients had genetic tests and listening tests, of which 251 were diagnosed with NSHL. In addition, we used whole-exome sequencing (WES) in a patient who has a significant family history of HHL but negative for gene chip testing, as well as in his family members. RESULT: Among of 251 patients, Nucleotide changes were found in 63 cases (25.09%), including 34 located in GJB2(13.5%, including 235delC and 299_300delAT), 13 located in SLC26A4(5.18%, including c.919-2G > A and 2168 A > G), 1 located in GJB3(0.4%,538C > T) and 16 located in mtDNA12SrRNA (6.37%,1555 A > G). In addition, we discuss the process of identifying novel PLS1 mutations from 251 patients. CONCLUSION: Our results demonstrate the conventional deafness gene mutation in 251 NSHL patients in Fujian, China. Compared with the other area of China, we have a lower detection rate, but GJB2 235delC remains the most common mutation in Fujian. In addition, we discuss the process of discovering novel mutation locus for deafness, which provides an understanding for deafness diagnosis and genetic testing.

Next-generation sequencing for genetic testing of hearing loss populations.

BACKGROUND AND AIMS: Hearing loss is a common sensorineural disease with genetic heterogeneity. More than 140 genes are known to cause hereditary hearing loss. We aim to uncover the etiologies of hearing loss and provide patients with reasonable reproductive choices. MATERIALS AND METHODS: Total 825 participants were recruited, including 74 individuals, 47 couples, and 219 families, to identify the molecular etiologies of hearing loss using next-generation sequencing (NGS). Novel mutations were verified with a minigene splicing assay and the construction of three-dimensional protein models. RESULTS: A positive molecular diagnosis was obtained for 244 patients, a rate of 63.05 %. Total 470 mutations were identified in 18 causative genes in positive patients. The most common genes mutated were GJB2 and SLC26A4. 47 novel mutations were identified. Further analysis predicted that two splicing mutations would cause abnormal mRNA splicing and three missense mutations would affect the protein structure. The results of prenatal diagnosis showed that the genotypes of 15 fetuses were the same as the probands. CONCLUSION: Our findings expand the mutation spectrum of hearing loss and highlight the importance of genetic diagnosis and prenatal diagnosis to allow accurate and personalized guidance for those at high risk of deafness.

Longitudinal Analysis of Early Hearing Detection and Intervention Program Performance.

OBJECTIVES: Early hearing detection and intervention (EHDI) is a newborn hearing screening system created to detect infants with hearing loss (HL) and intervene to reduce language and communication impairment. Early hearing detection (EHD) consists of three sequential stages: identification, screening, and diagnostic testing. This study longitudinally reviews each stage of EHD in each state and proposes a framework to improve utilization of EHD data. DESIGN: A retrospective public database review was conducted, accessing publicly available data from the Centers for Disease Control and Prevention. Summary descriptive statistics were utilized to generate a descriptive study of EHDI programs in each U.S. state from 2007 to 2016. RESULTS: Data over 10 years from 50 states as well as Washington, DC were included in this analysis, creating up to 510 data points per analysis. Hundred percent (85 to 105) (median [min to max]) of newborns were identified by and entered EHDI programs. Ninety-eight percent (51 to 100) of identified infants completed screening. Of the infants who screened positive for HL, the proportion that received diagnostic testing was 55% (1 to 100). The overall proportion of infants who failed to complete EHD was 3% (1 to 51). Of the infants who fail to complete EHD 70% (0 to 100) are from missed screenings, 24% (0 to 95) are from missed diagnostic testing, and 0% (0 to 93) are from missed identification. Although there are more infants missed at screening, it was estimated, with limitations, that there is an order of magnitude more infants with HL among those who did not complete diagnostic testing compared with those who did not complete screening. CONCLUSIONS: Analysis demonstrates high completion rates at both identification and screening stages, whereas the diagnostic testing stage demonstrates low and highly variable completion rates. The low completion rates at diagnostic testing create a bottleneck in the EHD process and the large variability impedes the comparison of HL outcomes across states. Analysis also demonstrates that among all stages of EHD, whereas the largest number of infants are missed at screening, the largest number of children with HL are likely missed at diagnostic testing. Therefore, a focus by individual EHDI programs on addressing causes of low diagnostic testing completion rates would yield the greatest increase in the identification of children with HL. Potential causes of low diagnostic testing completion rates are further discussed. Finally, a new vocabulary framework is proposed to facilitate further study of EHD outcomes.

Factors that influence health service access in deaf and hard-of-hearing children: a narrative review.

OBJECTIVES: Early diagnosis and intervention of deaf and hard-of-hearing (DHH) children leads to improved language and psychosocial outcomes. However, many child, parent and provider related factors can influence access to early intervention services, including hearing devices. This narrative review aims to explore factors that influence health service access in DHH children. DESIGN: A systematic search was conducted to identify articles that explored factors that influenced health service access in DHH children in countries with Universal Newborn Hearing Screening, published between 2010 and 2022. STUDY SAMPLES: Fifty-nine articles met the inclusion criteria for data extraction. This included 4 systematic reviews, 2 reviews, 39 quantitative and 5 mixed methods studies and 9 qualitative studies. RESULTS: The identified factors were grouped into the following themes: (a) demographic factors, (b) family related factors, (c) child related factors, (d) factors specific to hearing devices, (e) service delivery, f) telehealth and (g) COVID-19. CONCLUSION: This review provided a comprehensive summary of multiple factors that affect access to health services in DHH children. Psychosocial support, consistent clinical advice, allocation of resources to rural communities and use of telehealth are possible ways to address barriers and improve health service access.

A cost-effectiveness analysis of pre-pregnancy genetic screening for deafness: an empirical study in China.

Objectives: This research aims to assess the effectiveness and cost-effectiveness of pre-pregnancy deafness screening policies. Methods: Married couples from Shanghai, Beijing, and Suzhou in China were enrolled. We conducted high-throughput, pre-pregnancy genetic screenings for deafness in women and their partners. We compared the cost-effectiveness of deafness genetic screening with the status quo. The two-step screening (wife then partner) and following treatments and interventions were included in the decision tree model. We conducted a cost-effectiveness analysis based on the decrease in deaf newborns, healthy newborn births, and cost-utility analysis of pre-pregnancy deafness genetic screening separately. Cost, utility, and probability data used in the three models were collected from a survey combined with literature and expert consultants. A 5% discount rate and a series of one-way sensitivity analyses along with a Monte Carlo simulation were used to test the reliability of this research. Results: Between Jan 1, 2019, and Dec 31, 2021, we recruited 6,200 females and 540 male spouses from community health service centers in Shanghai, Beijing, and Suzhou. The incremental cost-effectiveness ratio (ICER) for reducing deaf newborn births was USD 32,656 per case and USD 1,203,926 per case for increasing one healthy newborn birth. This gap exists because of the overall decrease of newborn births. From the perspective of the whole society, deafness genetic screening is not cost-effective for reducing the overall quality-adjusted life years (QALY) in the population. Discussion: Pre-pregnancy genetic testing is effective in decreasing the occurrence of congenital deafness. It is a cost-saving measure when compared with the costs of future medical expenditure and income loss for the affected families. However, such screening and preventive avoidance of pregnancy will decrease the population size and QALY. Only post-screening ART with PGT was shown to increase the birth of healthy newborns. Focusing on key groups such as premature births or consanguineous couples may improve the societal effects of screening.

[Prospective comparative analysis of cochlear implant patients with single-sided deafness and asymmetric hearing loss with regard to health-related quality of life, tinnitus distress and psychological comorbidities]. / Prospektive Vergleichsanalyse von CI-Patienten mit einseitiger Taubheit und asymmetrischem Hörverlust hinsichtlich der gesundheitsbezogenen Lebensqualität, Tinnitusbelastung und psychischen Komorbiditäten.

BACKGROUND: Patients with single-sided deafness (SSD) and asymmetric hearing loss (AHL) are increasingly being treated with cochlear implants (CI) due to the demonstrated improvements in auditory abilities and quality of life. To date, there are few published studies in which these two groups are comparatively studied. The aim of the current study was to examine which factors differ between those two patient groups, especially preoperatively. METHODS: A secondary analysis of the previously published raw data of 66 prospectively recruited CI patients (21 SSD/45 AHL) was performed. In addition to the hearing outcome, tinnitus distress (tinnitus questionnaire), health-related quality of life (Nijmegen Cochlear Implant Questionnaire, NCIQ), stress (Perceived Stress Questionnaire, PSQ), and psychological comorbidities (General Depression Scale, ADS­L and Generalized Anxiety Disorder scale, GAD-7) were assessed in SSD and AHL patients pre- and postoperatively. RESULTS: Preoperatively, SSD patients showed significantly higher scores in the NCIQ subdomains "elementary" and "advanced sound perception" than the AHL group. Stress (PSQ) and anxiety symptoms (GAD-7) were significantly higher preoperatively in SSD patients than in AHL patients. After CI, these differences were strongly reduced, with minimal differences being detectable between the groups in the investigated domains postoperatively. CONCLUSION: SSD and AHL patients differ significantly preoperatively in terms of their subjective hearing assessment and psychosocial parameters. In SSD patients, psychological stress factors may have a stronger impact on the quality of life than in AHL patients. These aspects should be taken into account in the preoperative counseling and postoperative rehabilitation.

Case report: mitochondrial diabetes mellitus in a Chinese family due to m.3243A>G.

OBJECTIVES: Mitochondrial diabetes mellitus is caused by dysfunctional mitochondria and is often misdiagnosed because of its various clinical manifestations. It's even rarer in children, and without a clear family history of diabetes with hearing loss, it's often difficult to diagnose. CASE PRESENTATION: This is a case study of a family with maternally inherited diabetes mellitus and deafness (MIDD). The proband was an adolescent girl with diabetes with a family history of type 2 diabetes (T2DM) for three generations. Family members have undetected hearing impaired. The proband could not be diagnosed with type 1 diabetes (T1DM) or T2DM. Therefore, whole exome and mitochondrial gene sequencing was performed, which identified an m.3243A>G mutation in the mitochondrial DNA. CONCLUSIONS: This suggests that we should be alert to the possibility of hereditary diabetes, especially mitochondrial diabetes in patients with atypical diabetes. A thorough physical examination is very important. What is new: (1) Mitochondrial diabetes in childhood may not be accompanied by deafness even with highly heteroplasmy levels. (2) In MIDD patients, sometimes hearing loss cannot be perceived, which requires us to conduct detailed physical examinations and related examinations. (3) The use of metformin in MIDD patients did not have adverse consequences.