Multicenter study on the genetic screening and diagnosis of deafness in China
| ISRCTN | ISRCTN10768387 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10768387 |
| Secondary identifying numbers | ChiCTR1800018223 |
- Submission date
- 27/05/2020
- Registration date
- 16/06/2020
- Last edited
- 11/06/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Genetic Diseases
Plain English Summary
Background and study aims
According to the data of the national survey in 2006, there are about 27.8 million hearing and speech-disabled people in China, and about 700,000-800,000 hearing-impaired children under 7 years old. One in every 500 newborns has bilateral permanent deafness. Before the age of 5, the incidence of deafness increases to 2.7%, and to 3.5% in adolescence. Research shows that more than 60% of pre-lingual deafness is caused by genetic factors, and the rest is caused by environment or other unknown genetic factors.
As the first genetic hearing loss molecular diagnosis center in China, the genetic deafness molecular diagnosis center of PLA General Hospital has been established for 15 years. A series of achievements have been made in the research of the causes of deafness, discovery of new genes, the molecular epidemiology of deafness in the Chinese population, clinical gene diagnosis and prenatal diagnosis.
The emergence of next-generation sequencing has achieved high throughput and low cost, which brings a broad prospect for the field of gene diagnosis. At present, many gene testing institutions in China have carried out deafness gene testing services, mainly for the most common 3-4 hotspot mutation chips of deafness gene in Chinese population, and 129-167 deafness gene sequencing services. According to the research results of the researchers' center, four common gene mutations can explain about 40% of the causes of deafness, while the detection rate can rise to about 50% - 55% when the detection range is extended to more than 129 deafness genes by high-throughput sequencing technology. Although the improvement of diagnosis rate makes more deaf families or high-risk families obtain genetic consultation and prevention guidance, the promotion and implementation of deafness gene diagnosis and prenatal diagnosis in China still face a series of problems. The testing quality level of testing institutions is uneven, with a lack of standards. The testing report has not yet formed a standard, and the interpretation of variants is not clear. Testing institutions and clinical doctors give inaccurate genetic consultations. There is a lack of a referral and consultation system and process for difficult cases, and a lack of a biological database for deafness in China. The above deficiencies have greatly affected the summary of deafness molecular big data, the guidance of deafness family reproduction and the accurate treatment evaluation of deaf patients. Therefore, the PLA general hospital takes the lead in launching the clinical multicenter research project of deafness gene diagnosis, cooperating with domestic deafness gene testing institutions such as the medical institutions of major provinces and autonomous regions, MyGenostics Inc.; GrandOmics Inc.; WuXi NextCODE Inc.; Capital Genomics Inc. This multicenter study aims to draw a gene map of Chinese people by collecting 10,000 genetic samples; develop clinical consensus/guidelines for the diagnosis of genetic deafness; standardize deafness gene test, report interpretation and genetic consultation; and upgrade the deafness gene test panel.
Who can participate?
Patients with congenital hearing loss or late-onset hearing loss and their families, or patients with acquired sensorineural hearing loss and their families, and hearing normal individuals with a family history of deafness.
What does the study involve?
Patients will take hearing tests, a CT scan and, if necessary, a general examination (thyroid ultrasound, kidney ultrasound, electrocardiogram, chest, abdomen, limbs X-ray, cranial MRI, etc). The researchers collect patients' and their family's medical record information, and collect their blood samples. The genetic testing institution completes the gene test and preliminary data analysis, and the original data will be sent to the designated cloud platform of multicenter for verification and further analysis. The test report will be issued by the testing institution, and approved by the PLA General Hospital and/or qualified sub-centre experts. The PLA General Hospital and the clinical experts of the sending unit will jointly provide patients with genetic consultation. For the cases with suspected pathogenic mutations, the testing institution will provide follow-up research programs. For the cases with no or suspected pathogenic mutation, the leading units of multiple centers will analyze the data again, and discuss the follow-up research plan through regular case discussion and academic activities.
What are the possible benefits and risks of participating?
Taking part in this study can help patients to reduce the risk of deafness in their offspring. It should be noted that this study can not completely exclude the risk of deafness in the next generation, such as pregnancy infection, other environmental factors or rare unknown deafness caused by genetic defects. If the report result is negative, senior experts will re-analyze the report, except for false negatives. If it is positive, it will be verified free of charge, except for false positives. Difficult and complex cases will be provided with priority referral and consultation channels.
Where is the study run from?
Genetic Deafness Molecular Diagnosis Center, PLA General Hospital, Beijing, China
When is the study starting and how long is it expected to run for?
September 2018 to August 2022
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Prof. Pu Dai
daipu301@vip.sina.com
Prof. Yongyi Yuan
yyymzh@163.com
Contact information
Scientific
Fuxing Road 28
Beijing
100853
China
| Phone | +86 (0)13910213511 |
|---|---|
| daipu301@vip.sina.com |
Scientific
Fuxing Road 28
Beijing
100853
China
| Phone | +86 (0)13811502776 |
|---|---|
| yyymzh@163.com |
Scientific
Fuxing Road 28
Beijing
100853
China
| Phone | +86 (0)18515902036 |
|---|---|
| imjd@163.com |
Study information
| Study design | Multicenter observational epidemiological study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Epidemiological study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Clinical demonstration for three-level prevention intervention of birth defect on monogenic disease (deafness) |
| Study hypothesis | The main purpose of this multicenter study is to draw a gene map of Chinese people by collecting 10,000 genetic deafness samples and develop clinical consensus/guidelines for the diagnosis of genetic deafness. |
| Ethics approval(s) | Approved 26/7/2018, ethical review board of PLA General Hospital (Fuxing Road 28, Beijing, China; +86 (0)10 66937166; 301irb@sina.com), ref: S2018-088-01 |
| Condition | Genetic deafness |
| Intervention | The patients and their families will provide blood samples. Next-generation sequencing and Sanger sequencing will be carried out on the samples. The testing institution will analyze preliminary data. The PLA General Hospital and the clinical experts of the sending unit will jointly provide patients with genetic consultation. For the cases with suspected pathogenic mutations, the testing institution will provide follow-up research programs. For the cases with no or suspected pathogenic mutation, the leading units of multiple centers will analyze the data again, and discuss the follow-up research plan. |
| Intervention type | Other |
| Primary outcome measure | 1. Number of cases in the database of genetic deafness patients in China at 5 years 2. Gene map of genetic deafness patients in China measured using the coverage of pathogenic variant on genetic deafness in the public database at 5 years |
| Secondary outcome measures | 1. Genetic deafness panel measured using coverage and accuracy of pathogenic variant on genetic deafness in the public database at 5 years 2. Guidelines of screening and diagnosis for genetic deafness patients in China measured using the published journal articles at 5 years |
| Overall study start date | 09/01/2018 |
| Overall study end date | 31/08/2022 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | All |
| Sex | Both |
| Target number of participants | 10000 |
| Participant inclusion criteria | 1. Congenital hearing loss or late-onset hearing loss and their families 2. Patients with congenital malformation of auditory organ and their families 3. Acquired sensorineural hearing loss patients and their families 4. Hearing normal individuals with a family history of deafness |
| Participant exclusion criteria | 1. The patients and their families who refused to participate in the program after receiving the education by doctors 2. The patients with deafness caused by non-genetic factors were definitely diagnosed |
| Recruitment start date | 09/01/2018 |
| Recruitment end date | 31/08/2022 |
Locations
Countries of recruitment
- China
Study participating centres
Beijing
100853
China
Beijing
100029
China
Beijing
100088
China
Beijing
100045
China
Beijing
100029
China
Beijing
100730
China
Beijing
100034
China
Beijing
100191
China
Beijing
100032
China
Beijing
100050
China
Shanghai
200011
China
Fuzhou
350001
China
Wuhan
430022
China
Hefei
230001
China
Changsha
410008
China
Guangzhou
510515
China
Guangzhou
511400
China
Tianjin
300192
China
Zhengzhou
450000
China
Zhengzhou
450003
China
Shijiazhuang
050000
China
Tangshan
63017
China
Shijiazhuang
050030
China
Jinan
250022
China
Jinan
250000
China
Nanjing
210000
China
Zhenjiang
212001
China
Guiyang
550004
China
Kunming
650032
China
Lanzhou
730030
China
Xian
710032
China
Hefei
230000
China
Hefei
230013
China
Hefei
230601
China
Changchun
130041
China
Shenyang
110032
China
Yanji
100191
China
Shenyang
110011
China
Shenyang
110001
China
Hangzhou
310003
China
Liuzhou City
545001
China
Nanning City
530000
China
Taiyuan City
030001
China
Urumqi City
830001
China
Xining
810007
China
Yinchuan
750004
China
Hohhot
010000
China
Nanchang
330006
China
Chongqing
630038
China
Guangzhou
510317
China
Shenzhen
518001
China
Ningbo
315031
China
Shaoxing
312000
China
Ningbo
315010
China
Hanzhou
310006
China
Hanzhou
310006
China
Zhengzhou
450007
China
Qingdao
266034
China
YInchuan
750002
China
Guangzhou
510080
China
Lanzhou
730050
China
Beijing
100080
China
Shenyang
110031
China
Zhengzhou
450014
China
Haikou
570102
China
Jinan
250033
China
Suzhou
215006
China
Suzhou
215021
China
Beijing
100053
China
Baoding
071051
China
Qingdao
250012
China
Qingdao
266000
China
Shijiazhuang
050082
China
Sponsor information
Hospital/treatment centre
Fuxing Road 28
Beijing
100853
China
| Phone | +86 (0)10-66938119 |
|---|---|
| daipu301@vip.sina.com | |
| Website | http://www.plagh.cn |
"ROR" |
https://ror.org/04gw3ra78 |
Funders
Funder type
Other
No information available
Results and Publications
| Intention to publish date | 01/09/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. Peer-reviewed scientific journals 2. Conference presentation 3. Publication on website |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Pu Dai (daipu301@vip.sina.com), Prof. Yongyi Yuan (yyymzh@163.com) and Dr Bo Gao (imjd@163.com). The next-generation sequencing data for genetic deafness can be shared with groups who would like to participate in the trial during the research, and all data will be submitted to the public database (e.g ClinVar) in 3 years after the the end of the trial. |
Editorial Notes
10/06/2020: Trial's existence confirmed by Chinese PLA General Hospital Ethics Committee.
