{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:33:09Z","timestamp":1779881589519,"version":"3.53.1"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Sensorineural hearing impairment is a common sensory deficit in children and more than 50% of these cases are caused by genetic etiologies, that is, hereditary hearing impairment (HHI). Recent advances in genomic medicine have revolutionized the diagnostics of, and counseling for, HHI, including preimplantation genetic diagnosis (PGD), thus providing parents-to-be with better reproductive choices. Over the past decade, we have performed PGD using the amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) technique in 11 couples with a history of HHI, namely eight with GJB2 variants, one with OTOF variants, one with SLC26A4 variants, and one with an MITF variant. We demonstrated that PGD can be successfully applied to HHI of different inheritance modes, namely autosomal dominant or recessive, and phenotypes, namely syndromic or non-syndromic HHI. However, certain ethical concerns warrant scrutiny before PGD can be widely applied to at-risk couples with a history of HHI.<\/jats:p>","DOI":"10.3390\/diagnostics11122395","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T02:50:18Z","timestamp":1639968618000},"page":"2395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Preimplantation Genetic Diagnosis in Hereditary Hearing Impairment"],"prefix":"10.3390","volume":"11","author":[{"given":"Hsin-Lin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, National Taiwan University Hospital, Cancer Center Branch, Taipei 10672, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Hsuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, National Taiwan University Hospital Yunlin Branch, Yunlin 63247, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ting","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, National Taiwan University Hospital, Taipei 10002, Taiwan"},{"name":"Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 50046, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Fang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4925-7101","authenticated-orcid":false,"given":"Gwo-Chin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Ping","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Yang","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 50046, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei 10041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5047-2204","authenticated-orcid":false,"given":"Chen-Chi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, National Taiwan University Hospital, Taipei 10002, Taiwan"},{"name":"Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 30261, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5076-2917","authenticated-orcid":false,"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"},{"name":"Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei 10041, Taiwan"},{"name":"Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan"},{"name":"Department of Biomedical Science, Dayeh University, Changhua 51591, Taiwan"},{"name":"Medical College Provisional Office, National Chung Hsing University, Taichung 40227, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.otc.2015.07.004","article-title":"Diagnostic Evaluation of Children with Sensorineural Hearing Loss","volume":"48","author":"Prosser","year":"2015","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1001\/jama.2020.17647","article-title":"Hearing Loss in Children","volume":"324","author":"Lieu","year":"2020","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16094","DOI":"10.1038\/nrdp.2016.94","article-title":"Congenital hearing loss","volume":"3","author":"Korver","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/mrdd.10068","article-title":"Nongenetic causes of hearing loss","volume":"9","author":"Roizen","year":"2003","journal-title":"Ment. Retard. Dev. Disabil. Res. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S0140-6736(05)71047-3","article-title":"Sensorineural hearing loss in children","volume":"365","author":"Smith","year":"2005","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/344768a0","article-title":"Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification","volume":"344","author":"Handyside","year":"1990","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e5908","DOI":"10.1136\/bmj.e5908","article-title":"Preimplantation genetic testing","volume":"345","author":"Brezina","year":"2012","journal-title":"BMJ"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/humrep\/deq231","article-title":"ESHRE PGD consortium best practice guidelines for amplification-based PGD","volume":"26","author":"Harton","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.gene.2014.07.039","article-title":"Validating a rapid, real-time, PCR-based direct mutation detection assay for preimplantation genetic diagnosis","volume":"548","author":"Chen","year":"2014","journal-title":"Gene"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.tjog.2011.10.012","article-title":"Preimplantation and prenatal genetic diagnosis of aromatic L-amino acid decarboxylase deficiency with an amplification refractory mutation system-quantitative polymerase chain reaction","volume":"50","author":"Kuo","year":"2011","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1086\/302261","article-title":"Clear Correlation of Genotype with Disease Phenotype in Very\u2013Long-Chain Acyl-CoA Dehydrogenase Deficiency","volume":"64","author":"Andresen","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s10815-009-9335-5","article-title":"Preimplantation genetic diagnosis (PGD) for nonsyndromic deafness by polar body and blastomere biopsy","volume":"26","author":"Altarescu","year":"2009","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1159\/000284349","article-title":"Preimplantation Genetic Diagnosis (Embryo Screening) for Enlarged Vestibular Aqueduct due toSLC26A4Mutation","volume":"15","author":"Wu","year":"2010","journal-title":"Audiol. Neurotol."},{"key":"ref_14","first-page":"1708","article-title":"The first successful application of preimplantation genetic diagnosis for hearing loss in Iran","volume":"64","author":"Yazdi","year":"2018","journal-title":"Cell. Mol. Biol."},{"key":"ref_15","first-page":"4296","article-title":"Successful preimplantation genetic diagnosis by targeted next-generation sequencing on an ion torrent personal genome machine platform","volume":"15","author":"Hao","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.rbmo.2015.08.017","article-title":"Karyomapping allows preimplantation genetic diagnosis of a de-novo deletion undetectable using conventional PGD technology","volume":"31","author":"Sarasa","year":"2015","journal-title":"Reprod. Biomed. Online"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/humrep\/deg100","article-title":"Extending preimplantation genetic diagnosis: The ethical debate: Ethical issues in new uses of preimplantation genetic diagnosis","volume":"18","author":"Robertson","year":"2003","journal-title":"Hum. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1017\/S0963180109990272","article-title":"Choosing Deafness with Preimplantation Genetic Diagnosis: An Ethical Way to Carry on a Cultural Bloodline?","volume":"19","author":"Camporesi","year":"2009","journal-title":"Camb. Q. Health Ethics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1177\/1084713809356701","article-title":"Achieving Developmental Synchrony in Young Children with Hearing Loss","volume":"13","author":"Mellon","year":"2009","journal-title":"Trends Amplif."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/00125817-200207000-00004","article-title":"GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: A HuGE review","volume":"4","author":"Kenneson","year":"2002","journal-title":"Genet. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1136\/jmg.2003.013896","article-title":"A genotype-phenotype correlation for GJB2 (connexin 26) deafness","volume":"41","author":"Cryns","year":"2004","journal-title":"J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1001\/archoto.2009.202","article-title":"Audiologic phenotype and progression in GJB2 (Connexin 26) hearing loss","volume":"136","author":"Kenna","year":"2010","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E34","DOI":"10.1002\/lary.24332","article-title":"GJB2-associated hearing loss: Systematic review of worldwide prevalence, genotype, and auditory phenotype","volume":"124","author":"Chan","year":"2013","journal-title":"Laryngoscope"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/AUD.0000000000000742","article-title":"Prediction Model for Audiological Outcomes in Patients with GJB2 Mutations","volume":"41","author":"Chen","year":"2020","journal-title":"Ear Hear."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3345\/kjp.2019.00808","article-title":"Genetic tests by next-generation sequencing in children with developmental delay and\/or intellectual disability","volume":"63","author":"Han","year":"2020","journal-title":"Clin. Exp. Pediatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3389\/fped.2020.00373","article-title":"Genomic Diagnosis for Pediatric Disorders: Revolution and Evolution","volume":"8","author":"LaLonde","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wu, C.-C., Tsai, C.-Y., Lin, Y.-H., Chen, P.-Y., Lin, P.-H., Cheng, Y.-F., Wu, C.-M., Lin, Y.-H., Lee, C.-Y., and Erdenechuluun, J. (2019). Genetic Epidemiology and Clinical Features of Hereditary Hearing Impairment in the Taiwanese Population. Genes, 10.","DOI":"10.3390\/genes10100772"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1093\/jlb\/lsx038","article-title":"The known unknown: The challenges of genetic variants of uncertain significance in clinical practice","volume":"4","year":"2017","journal-title":"J. Law Biosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.ejmg.2017.07.016","article-title":"Reporting practices for variants of uncertain significance from next generation sequencing technologies","volume":"60","author":"Vears","year":"2017","journal-title":"Eur. J. Med. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/jgc4.1075","article-title":"Patients\u2019 perspectives of variants of uncertain significance and strategies for uncertainty management","volume":"28","author":"Makhnoon","year":"2019","journal-title":"J. Genet. Couns."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/gm475","article-title":"Preimplantation genetic diagnosis guided by single-cell genomics","volume":"5","author":"Esteki","year":"2013","journal-title":"Genome Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"522","DOI":"10.5603\/GP.2016.0037","article-title":"Current methods for preimplantation genetic diagnosis","volume":"87","author":"Liss","year":"2016","journal-title":"Ginekol. Pol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/12\/2395\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:52:16Z","timestamp":1760169136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/12\/2395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,20]]},"references-count":32,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["diagnostics11122395"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11122395","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,20]]}}}