{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:49:44Z","timestamp":1791978584590,"version":"4.4.0"},"reference-count":44,"publisher":"Cold Spring Harbor Laboratory","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>Infants suffering from life-threatening apnea, stridor, cyanosis, and increased muscle tone may often be misdiagnosed with infantile seizures and inappropriately treated because of lack and delay in genetic diagnosis. Here, we report a patient with increased muscle tone after birth and hypertonic attacks with life-threatening apnea but no epileptiform patterns in EEG recordings. We identified novel compound heterozygous variants in <jats:italic>SLC6A5<\/jats:italic> (NM_004211.4:c.[1429T &gt; C];[1430delC]) by trio whole-exome sequencing, containing a base deletion inherited by the asymptomatic mother leading to a frameshift (c.1430delC, p.Ser477PhefsTer9) and a de novo base exchange leading to an amino acid change (c.1429T &gt; C, p.Ser477Pro). To date, there are four known disease-associated genes for primary hyperekplexia, all of which are involved in the functioning of glycinergic synapses. <jats:italic>SLC6A5<\/jats:italic> encodes the sodium- and chloride-dependent glycine transporter 2 (GlyT2), which recaptures glycine, a major inhibitory transmitter in the brainstem and spinal cord. The diagnosis altered the patient's medical care to his benefit because <jats:italic>SLC6A5<\/jats:italic> mutations with rather benign courses of hyperekplexia may be spared of needless pharmacotherapy. Symptoms eventually decreased in frequency until about once in 2 mo at 2 yr age. We present the first report of halting hyperekplexia episodes by maternal soothing in multiple instances. We highlight the importance of clarifying the genetic diagnosis by rapid next-generation sequencing techniques in this group of infantile apneic attacks with hyperekplexia due to the broad differential diagnoses.<\/jats:p>","DOI":"10.1101\/mcs.a004465","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T20:25:22Z","timestamp":1570825522000},"page":"a004465","source":"Crossref","is-referenced-by-count":17,"title":["Novel mutations in <i>SLC6A5<\/i> with benign course in hyperekplexia"],"prefix":"10.1101","volume":"5","author":[{"given":"Hormos Salimi","family":"Dafsari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Kawalia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanne","family":"Sprute","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mert","family":"Karakaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Malenica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Herkenrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"N\u00fcrnberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Motameny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Thiele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebahattin","family":"Cirak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2019,10,11]]},"reference":[{"key":"2021112506195949000_5.6.a004465.1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000130"},{"key":"2021112506195949000_5.6.a004465.2","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a002139"},{"key":"2021112506195949000_5.6.a004465.3","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22493"},{"key":"2021112506195949000_5.6.a004465.4","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00347"},{"key":"2021112506195949000_5.6.a004465.5","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-7-2"},{"key":"2021112506195949000_5.6.a004465.6","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-017-0418-0"},{"key":"2021112506195949000_5.6.a004465.7","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.143.5.1041"},{"key":"2021112506195949000_5.6.a004465.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-018-1929-5"},{"key":"2021112506195949000_5.6.a004465.9","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds498"},{"key":"2021112506195949000_5.6.a004465.10","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.150823"},{"key":"2021112506195949000_5.6.a004465.11","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv332"},{"key":"2021112506195949000_5.6.a004465.12","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh340"},{"key":"2021112506195949000_5.6.a004465.13","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007185"},{"key":"2021112506195949000_5.6.a004465.14","doi-asserted-by":"publisher","DOI":"10.1186\/s40348-016-0050-x"},{"key":"2021112506195949000_5.6.a004465.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.08.005"},{"key":"2021112506195949000_5.6.a004465.16","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700163R"},{"key":"2021112506195949000_5.6.a004465.17","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(90)90149-A"},{"key":"2021112506195949000_5.6.a004465.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2008.06.005"},{"key":"2021112506195949000_5.6.a004465.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1813520115"},{"key":"2021112506195949000_5.6.a004465.20","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812460094"},{"key":"2021112506195949000_5.6.a004465.21","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1584084"},{"key":"2021112506195949000_5.6.a004465.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126321"},{"key":"2021112506195949000_5.6.a004465.23","doi-asserted-by":"publisher","DOI":"10.1101\/gr.138115.112"},{"key":"2021112506195949000_5.6.a004465.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcp.2019.03.002"},{"key":"2021112506195949000_5.6.a004465.25","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-44"},{"key":"2021112506195949000_5.6.a004465.26","doi-asserted-by":"publisher","DOI":"10.1126\/science.252.5009.1162"},{"key":"2021112506195949000_5.6.a004465.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2009.02.017"},{"key":"2021112506195949000_5.6.a004465.28","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12617"},{"key":"2021112506195949000_5.6.a004465.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01390-8"},{"key":"2021112506195949000_5.6.a004465.30","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.37"},{"key":"2021112506195949000_5.6.a004465.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27212-8"},{"key":"2021112506195949000_5.6.a004465.32","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts526"},{"key":"2021112506195949000_5.6.a004465.33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153253"},{"key":"2021112506195949000_5.6.a004465.34","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100569"},{"key":"2021112506195949000_5.6.a004465.35","doi-asserted-by":"publisher","DOI":"10.1038\/ng1814"},{"key":"2021112506195949000_5.6.a004465.36","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2021112506195949000_5.6.a004465.37","doi-asserted-by":"publisher","DOI":"10.1038\/ng1293-351"},{"key":"2021112506195949000_5.6.a004465.38","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000267"},{"key":"2021112506195949000_5.6.a004465.39","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12638"},{"key":"2021112506195949000_5.6.a004465.40","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(97)05378-1"},{"key":"2021112506195949000_5.6.a004465.41","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)95534-0"},{"key":"2021112506195949000_5.6.a004465.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.07.018"},{"key":"2021112506195949000_5.6.a004465.43","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp033"},{"key":"2021112506195949000_5.6.a004465.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2017.11.003"}],"container-title":["Molecular Case Studies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/mcs.a004465","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T14:20:09Z","timestamp":1637850009000},"score":1,"resource":{"primary":{"URL":"http:\/\/molecularcasestudies.cshlp.org\/lookup\/doi\/10.1101\/mcs.a004465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,11]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,12,13]]},"published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1101\/mcs.a004465"],"URL":"https:\/\/doi.org\/10.1101\/mcs.a004465","relation":{},"ISSN":["2373-2865","2373-2873"],"issn-type":[{"value":"2373-2865","type":"print"},{"value":"2373-2873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,11]]}}}