Deafness Gene Mutations in Newborns in the Foshan Area of South China With Bloodspot-Based Genetic Screening Tests

2020 ◽  
Vol 29 (2) ◽  
pp. 165-169
Author(s):  
Shunwang Cao ◽  
Yanhua Sha ◽  
Peifeng Ke ◽  
Tingting Li ◽  
Weixi Yuan ◽  
...  
Keyword(s):  
Gene Mutation ◽  
South China ◽  
Genetic Screening ◽  
Gene Mutations ◽  
Screening Tests ◽  
Premature Delivery ◽  
12S Rrna ◽  
High Birth Weight ◽  
Congenital Hearing Loss ◽  
Deafness Gene

Purpose The aim of this study was to determine the rate of deafness gene mutations in the Foshan area of South China. Method We enrolled the infants delivered in Foshan Maternity and Children's Healthcare Hospital. Deafness gene mutation was detected by HibriMax method. Our study tested 47,538 newborns within 3 days after birth, including 13 sites in four genes: GJB2 (c.35 del G, c.176 del 16, c.235 del C, c.299 del AT, c.155 del TCTG), GJB3 (c.583 C>T), SLC26A4 (c.2168 A>G, c.919-2 A>G, c.1299 C>T), and mtDNA 12S rRNA (m.1555 A>G, m.1494 C>T, m.12201 T>C, m.7445 A>G). The birth condition of infants was collected, including sex, low or high birth weight, twins, and premature delivery. Results In a total of 47,538 newborns, 1,415 were positively identified with deafness gene mutations. The total rate of the deafness gene mutation was 2.976%. The carrier rates of GJB2 (c.35 del G, c.176 del 16, c.235 del C, c.299 del AT, c.155 del TCTG), GJB3 (c.583 C>T), SLC26A4 (c.2168 A>G, c.919-2 A>G, c.1299 C>T), and mtDNA 12S rRNA (m.1555 A>G, m.1494 C>T, m.12201 T>C, m.7445 A>G) mutations were 0.000%, 0.048%, 1.422%, 0.185%, 0.000%, 0.076%, 0.116%, 0.755%, 0.160%, 0.187%, 0.021%, 0.000%, and 0.006%, respectively. Conclusions Our study showed that the c.235 del C GJB2 mutation was the leading deafness-related mutation in the Foshan area of South China. Deafness gene mutations screening in newborns detected by bloodspot-based genetic screening tests can help the diagnosis of newborn congenital hearing loss.

Concurrent Hearing and Genetic Screening of 18 001 Neonates with Hearing Diagnose in Nantong, China

2021 ◽  
Author(s):  
Jianhua Chen ◽  
Qingwen Zhu ◽  
Jingyu Li ◽  
Jing Wang ◽  
Wenjun Bian ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Early Detection ◽  
Genetic Screening ◽  
Late Onset ◽  
Gene Mutations ◽  
Hearing Screening ◽  
12S Rrna ◽  
Drug Induced ◽  
Dna Test ◽  
Deafness Gene

Abstract Objectives: Concurrent hearing and genetic screening of newborns is expected to play an important role in the early detection and diagnosis of congenital deafness, which triggers an intervention, as well as in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced hearing loss (HL).Methods: A Deafness Gene Variant Detection Array Kit covering fifteen variants in four genes was used to screen for deafness genes in 18001 infants.Results: A total of 108 neonates did not pass the second hearing screening. In addition, 912 (5.07%) screened positive for deafness-associated variants, including 78 (0.43%) genetically referred and 834 (4.63%) genetic deafness-associated variant carriers. Of the 912 screened positive cases, 880 passed the hearing screening, and 32 failed. A total of 62 (0.34%) cases carried the mtDNA 12S rRNA variants. A total of 108 cases did not pass the hearing screening and underwent a hearing diagnostic examination. An expanded DNA test identified 17 patients who possessed deafness gene mutations, increasing the detection rate to 5.16%.Conclusion: Early detection, diagnosis, and interventions are necessary for newborns who are susceptible to deafness. A good strategy is to use a small panel to quickly screen all subjects and then apply an extended panel to study the cause of deafness in affected patients.

scholarly journals Concurrent Hearing and Genetic Screening among Newborns in Ningbo, China

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Cao Guomei ◽  
Zhang Luyan ◽  
Dai Lingling ◽  
Huang Chunhong ◽  
Chen Shan
Keyword(s):  
Carrier Frequency ◽  
Genetic Variants ◽  
Genetic Screening ◽  
Gene Mutations ◽  
Hearing Screening ◽  
Screening Tests ◽  
Genomic Epidemiology ◽  
Deafness Gene ◽  
Hearing Test ◽  
Insight Into

Objective. To detect the carrier rates of deafness gene variants in populations in Ningbo and analyze the risk of hereditary hearing loss through concurrent hearing and genetic screening tests. Methods. Two thousand one hundred and seventy-four newborns were enrolled from November 2018 to August 2019. All subjects underwent hearing screening and newborn deafness genetic screening with 15 variants in 4 genes, and the positive sites were simultaneously verified by sequencing. Results. The total carrier rate of genetic variants in Ningbo reached 4.32%, when GJB2 c.235delC was the variant with the highest prevalence (2.12%), approximately accounting for 48.9% of the total carrier frequency. The carrier frequency of SLC26A4 c.919-2A>G was 0.87%, while the most common variant in mitochondrial DNA (mtDNA) MT-RNR1 gene was m.1555A>G, and its carrier frequency was 0.184%. In the OAE testing, 92 newborns passing hearing screening were tested positively for variants in 4 genes, and 2 of 42 newborns who failed in the first hearing test were found to mutate in 4 genes. Conclusion. Herein, the results concerning the carrier rates for deafness gene mutations of Ningbo population are reported. Our study is beneficial to the insight into the deafness genomic epidemiology for deafness genes in Ningbo population and provides the reference for healthcare in Ningbo.

scholarly journals Multi-Center in-Depth Screening of Neonatal Deafness Genes: Zhejiang, China

2021 ◽  
Vol 12 ◽  
Author(s):  
Luhang Cai ◽  
Ya Liu ◽  
Yaping Xu ◽  
Hang Yang ◽  
Lihui Lv ◽  
...  
Keyword(s):  
High Risk ◽  
Genetic Screening ◽  
Gene Mutations ◽  
Hearing Screening ◽  
Common Mutation ◽  
Multi Centre Study ◽  
High Risk Factors ◽  
Pathogenic Variants ◽  
Deafness Gene ◽  
Positive Rate

PurposeThe conventional genetic screening for deafness involves 9–20 variants from four genes. This study expands screening to analyze the mutation types and frequency of hereditary deafness genes in Zhejiang, China, and explore the significance of in-depth deafness genetic screening in newborns.MethodsThis was a multi-centre study conducted in 5,120 newborns from 12 major hospitals in the East-West (including mountains and islands) of Zhejiang Province. Concurrent hearing and genetic screening was performed. For genetic testing, 159 variants of 22 genes were screened, including CDH23, COL11A1, DFNA5, DFNB59, DSPP, GJB2, GJB3, KCNJ10, MT-RNR1, MT-TL1, MT-TS1, MYO15A, MYO7A, OTOF, PCDH15, SLC26A4, SOX10, TCOF1, TMC1, USH1G, WFS1, and WHRN using next-generation sequencing. Newborns who failed to have genetic mutations or hearing screening were diagnosed audiologically at the age of 6 months.ResultsA total of 4,893 newborns (95.57%) have passed the initial hearing screening, and 7 (0.14%) have failed in repeated screening. Of these, 446 (8.71%) newborns carried at least one genetic deafness-associated variant. High-risk pathogenic variants were found in 11 newborns (0.21%) (nine homozygotes and two compound heterozygotes), and eight of these infants have passed the hearing screening. The frequency of mutations in GJB2, GJB3, SLC26A4, 12SrRNA, and TMC1 was 5.43%, 0.59%, 1.91%, 0.98%, and 0.02%, respectively. The positive rate of in-depth screening was significantly increased when compared with 20 variants in four genes of traditional testing, wherein GJB2 was increased by 97.2%, SLC26A4 by 21% and MT-RNR1 by 150%. The most common mutation variants were GJB2c.235delC and SLC26A4c.919-2A > G, followed by GJB2c.299_300delAT. Homoplasmic mutation in MT-RNR1 was the most common, including m.1555A > G, m.961T > C, m.1095T > C. All these infants have passed routine hearing screening. The positive rate of MT-RNR1 mutation was significantly higher in newborns with high-risk factors of maternal pregnancy.ConclusionThe positive rate of deafness gene mutations in the Zhejiang region is higher than that of the database, mainly in GJB2c.235delC, SLC26A4 c.919-2A > G, and m.1555A > G variants. The expanded genetic screening in the detection rate of diseasecausing variants was significantly improved. It is helpful in identifying high-risk children for follow-up intervention.

scholarly journals The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome

2020 ◽  
Vol 21 (21) ◽  
pp. 8403
Author(s):  
Erkut Ilaslan ◽  
Renata Markosyan ◽  
Patrick Sproll ◽  
Brian J. Stevenson ◽  
Malgorzata Sajek ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Signaling Pathway ◽  
Gene Mutation ◽  
Gene Mutations ◽  
Androgen Insensitivity Syndrome ◽  
Homologous Gene ◽  
Gene Encoding ◽  
Androgen Insensitivity ◽  
Disorder Of Sexual Development ◽  
Partial Androgen Insensitivity Syndrome

Androgen insensitivity syndrome (AIS), manifesting incomplete virilization in 46,XY individuals, is caused mostly by androgen receptor (AR) gene mutations. Therefore, a search for AR mutations is a routine approach in AIS diagnosis. However, some AIS patients lack AR mutations, which complicates the diagnosis. Here, we describe a patient suffering from partial androgen insensitivity syndrome (PAIS) and lacking AR mutations. The whole exome sequencing of the patient and his family members identified a heterozygous FKBP4 gene mutation, c.956T>C (p.Leu319Pro), inherited from the mother. The gene encodes FKBP prolyl isomerase 4, a positive regulator of the AR signaling pathway. This is the first report describing a FKBP4 gene mutation in association with a human disorder of sexual development (DSD). Importantly, the dysfunction of a homologous gene was previously reported in mice, resulting in a phenotype corresponding to PAIS. Moreover, the Leu319Pro amino acid substitution occurred in a highly conserved position of the FKBP4 region, responsible for interaction with other proteins that are crucial for the AR functional heterocomplex formation and therefore the substitution is predicted to cause the disease. We proposed the FKBP4 gene as a candidate AIS gene and suggest screening that gene for the molecular diagnosis of AIS patients lacking AR gene mutations.

scholarly journals NPHS2 gene mutation, atopy, and gender as risk factors for steroid-resistant nephrotic syndrome in Indonesians

2011 ◽  
Vol 51 (5) ◽  
pp. 272 ◽  
Author(s):  
Dedi Rachmadi ◽  
Danny Hilmanto ◽  
Ponpon Ijradinata ◽  
Abdurahman Sukadi
Keyword(s):  
Risk Factors ◽  
Nephrotic Syndrome ◽  
Gene Mutation ◽  
Significant Risk ◽  
Gene Mutations ◽  
Male Gender ◽  
Amplification Refractory Mutation System ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Nphs2 Gene

Background Steroid-resistant nephrotic syndrome (SRNS) often develops into end stage renal disease. Previous studies have reported that NPHS2 gene mutation, gender, and atopic history are risk factors associated with SRNS. Interethnic, sociocultural, and environmental differences have also been suggested to affect these mutations.Objective To analyze possible risk factors for SRNS, including NPHS2 gene mutations (412C→T and 419delG), gender and atopic history, in Indonesian subjects with SRNS.Methods A case-control study with 153 subjects, consisting of 88 SRNS patients and 65 control subjects, was undertaken in 10 Indonesian teaching centre hospitals from September 2006 to December 2007. Analysis of the NPHS2 gene mutation in 412 C→T was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), while that for the NPHS2 gene mutation in 419delG was performed by restriction fragment length polymorphism (RFLP). Data was analyzed by multiple logistic regression.Results In our Indonesian subjects, the significant risk factors for SRNS were male gender (OR=2.21; CI 95%:1.07-4.56, P=0.036), NPHS2 412C→T gene mutation (OR=18.07; CI 95%:6.76-48.31, P<0.001), and NPHS2 419delG gene mutation (OR=4.55; CI 95%:1.66-12.47, P=0.003). However, atopic history was not a significant risk factor for SRNS (OR=1.807; CI 95%:0.642-5.086, P=0.262).Conclusion NPHS2 412C→T and 419delG gene mutations, as well as male gender are risk factors for SRNS in Indonesian subjects. Atopic history was not significantly associated with SRNS in our subjects. [Paediatr Indones. 2011;51:272-6].

scholarly journals The patient profile of individuals with Alpha-1 antitrypsine gene mutations at a referral center in Brazil

2018 ◽  
Vol 44 (5) ◽  
pp. 383-389
Author(s):  
Manuela Brisot Felisbino ◽  
Frederico Leon Arrabal Fernandes ◽  
Maria Cecília Nieves Maiorano de Nucci ◽  
Regina Maria de Carvalho Pinto ◽  
Emilio Pizzichini ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Respiratory Symptoms ◽  
Gene Mutations ◽  
Lower Lobe ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Referral Center ◽  
Patient Profile ◽  
Significant Difference ◽  
Alpha 1 Antitrypsin

ABSTRACT Objective: The clinical, functional, radiological and genotypic descriptions of patients with an alpha-1 antitrypsin (A1AT) gene mutation in a referral center for COPD in Brazil. Methods: A cross-sectional study of patients with an A1AT gene mutation compatible with deficiency. We evaluated the A1AT dosage and genotypic, demographic, clinical, tomographic, and functional characteristics of these patients. Results: Among the 43 patients suspected of A1AT deficiency (A1ATD), the disease was confirmed by genotyping in 27 of them. The A1AT median dosage was 45 mg/dL, and 4 patients (15%) had a normal dosage. Median age was 54, 63% of the patients were male, and the respiratory symptoms started at the age of 40. The median FEV1 was 1.37L (43% predicted). Tomographic emphysema was found in 77.8% of the individuals. The emphysema was panlobular in 76% of them and 48% had lower lobe predominance. The frequency of bronchiectasis was 52% and the frequency of bronchial thickening was 81.5%. The most common genotype was Pi*ZZ in 40.7% of participants. The other genotypes found were: Pi*SZ (18.5%), PiM1Z (14.8%), Pi*M1S (7.4%), Pi*M2Z (3.7%), Pi*M1I (3.7%), Pi*ZMnichinan (3.7%), Pi*M3Plowell (3.7%), and Pi*SF (3.7%). We did not find any significant difference in age, smoking load, FEV1, or the presence of bronchiectasis between the groups with a normal and a reduced A1AT dosage, neither for 1 nor 2-allele mutation for A1ATD. Conclusions: Our patients presented a high frequency of emphysema, bronchiectasis and bronchial thickening, and early-beginning respiratory symptoms. The most frequent genotype was Pi*ZZ. Heterozygous genotypes and normal levels of A1AT also manifested significant lung disease.

scholarly journals Children with 5′-end NF1 gene mutations are more likely to have glioma

2017 ◽  
Vol 3 (5) ◽  
pp. e192 ◽  
Author(s):  
Corina Anastasaki ◽  
Stephanie M. Morris ◽  
Feng Gao ◽  
David H. Gutmann
Keyword(s):  
Gene Mutation ◽  
Statistical Significance ◽  
Gene Mutations ◽  
Neurofibromatosis Type ◽  
Published Data ◽  
Data Sets ◽  
Nonsense Mutations ◽  
Data Set ◽  
Nf1 Gene ◽  
The Relationship

Objective:To ascertain the relationship between the germline NF1 gene mutation and glioma development in patients with neurofibromatosis type 1 (NF1).Methods:The relationship between the type and location of the germline NF1 mutation and the presence of a glioma was analyzed in 37 participants with NF1 from one institution (Washington University School of Medicine [WUSM]) with a clinical diagnosis of NF1. Odds ratios (ORs) were calculated using both unadjusted and weighted analyses of this data set in combination with 4 previously published data sets.Results:While no statistical significance was observed between the location and type of the NF1 mutation and glioma in the WUSM cohort, power calculations revealed that a sample size of 307 participants would be required to determine the predictive value of the position or type of the NF1 gene mutation. Combining our data set with 4 previously published data sets (n = 310), children with glioma were found to be more likely to harbor 5′-end gene mutations (OR = 2; p = 0.006). Moreover, while not clinically predictive due to insufficient sensitivity and specificity, this association with glioma was stronger for participants with 5′-end truncating (OR = 2.32; p = 0.005) or 5′-end nonsense (OR = 3.93; p = 0.005) mutations relative to those without glioma.Conclusions:Individuals with NF1 and glioma are more likely to harbor nonsense mutations in the 5′ end of the NF1 gene, suggesting that the NF1 mutation may be one predictive factor for glioma in this at-risk population.

scholarly journals Design and reporting considerations for genetic screening tests

2019 ◽  
Author(s):  
Jill Hagenkord ◽  
Birgit Funke ◽  
Emily Qian ◽  
Madhuri Hegde ◽  
Kevin B Jacobs ◽  
...  
Keyword(s):  
Genetic Screening ◽  
World Health ◽  
Screening Tests ◽  
Clinical Indication ◽  
Test Design ◽  
Design Strategies ◽  
Predictive Values ◽  
Inherited Diseases ◽  
Health Communities ◽  
Health Organization

Testing asymptomatic individuals for unsuspected conditions is not new to the medical and public health communities and protocols to develop screening tests are well-established. However, the application of screening principles to inherited diseases presents unique challenges. Unlike most screening tests, the natural history and disease prevalence of most rare inherited diseases in an unselected population are unknown. It is difficult or impossible to obtain a “truth set” cohort for clinical validation studies. As a result, it is not possible to accurately calculate clinical positive and negative predictive values for “likely pathogenic” genetic variants, which are commonly returned in genetic screening assays. In addition, many of the genetic conditions included in screening panels do not have clinical confirmatory tests. All of these elements are typically required to justify the development of a screening test, according to the World Health Organization screening principles. Nevertheless, as the cost of DNA sequencing continues to fall, more individuals are opting to undergo genomic testing in the absence of a clinical indication. Despite the challenges, reasonable estimates can be deduced and used to inform test design strategies. Here, we review test design principles and apply them to genetic screening.

scholarly journals Usher syndrome gene mutation spectrum in Russian patients

2020 ◽  
pp. 38-39
Author(s):  
М.Е. Иванова ◽  
А.М. Демчинский ◽  
В.С. Каймонов ◽  
И.В. Миронова ◽  
И.В. Володин ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Retinitis Pigmentosa ◽  
Gene Mutation ◽  
Clinical Diagnosis ◽  
Usher Syndrome ◽  
Gene Mutations ◽  
Mutation Spectrum ◽  
Initial Sample ◽  
New Mutations

Изучение спектра мутаций и совершенствование диагностики синдрома Ашера (СА) особо актуальны в связи с разрабатываемыми подходами к генной терапии заболевания. Среди 46 пациентов с признаками СА патогенные мутации выявлены нами у 40 (87%) пациентов. СА I и II типов определены у 26% и 57% пробандов исходной выборки, соответственно. У пациентов с СА I выявлены мутации в генах MYO7A (73%), CDH23 (7%), PCDH15 (7%), и USH1C (13%). Наибольшую частоту показала мутация MYO7A p.Q18*. Описано 6 новых мутаций в гене MYO7A, и две - в гене PCDH15. У пациентов с СА II выявлена 21 мутация гена USH2A, 5 из которых описаны впервые. Наибольшую частоту показала мутация USH2A p.W3955*. У двух пациентов выявлены мутации в генах несиндромального пигментного ретинита RHO и RPGR, что позволило уточнить клинический диагноз. Studying the mutation spectrum and improvement of molecular verification of the Usher syndrome (USH) are of particular relevance as gene therapy emerges. Among 46 patients with signs of Usher syndrome we identified mutations in 40 (85%) patients, establishing a diagnosis of USH1 and USH2 for 26% and 57% of the probands of the initial sample, respectively. Patients with USH1 showed mutations in the MYO7A (73%), CDH23 (7%), PCDH15 (7%), and USH1C (13%) genes. MYO7A p.Q18* mutation showed the highest frequency. We have identified 6 new mutations in the MYO7A gene, and 2 in the PCDH15 gene. In USH2 patients, 21 USH2A gene mutations were identified, 5 of which are novel. The USH2A mutation p.W3955* was most frequent. Two patients showed mutations in the non-syndromic retinitis pigmentosa genes RHO and RPGR, which made it possible to clarify the clinical diagnosis.

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