{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:39:05Z","timestamp":1762508345326,"version":"build-2065373602"},"reference-count":20,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Congenital myasthenic syndromes (CMSs) are caused by mutations in genes that encode proteins involved in the organization, maintenance, function, or modification of the neuromuscular junction. Among these, the collagenic tail of endplate acetylcholinesterase protein (COLQ; MIM 603033) has a crucial role in anchoring the enzyme into the synaptic basal lamina. Here, we report on the first case of a patient with a homozygous deletion affecting the last exons of the COLQ gene in a CMS patient born to consanguineous parents of Pakistani origin. Electromyography (EMG), electroencephalography (EEG), clinical exome sequencing (CES), and single nucleotide polymorphism (SNP) array analyses were performed. The subject was born at term after an uneventful pregnancy and developed significant hypotonia and dystonia, clinical pseudoseizures, and recurring respiratory insufficiency with a need for mechanical ventilation. CES analysis of the patient revealed a homozygous deletion of the COLQ gene located on the 3p25.1 chromosome region. The SNP-array confirmed the presence of deletion that extended from exon 11 to the last exon 17 with a size of 19.5 Kb. Our results add new insights about the underlying pathogenetic mechanisms expanding the spectrum of causative COLQ mutations. It is relevant, considering the therapeutic implications, to apply suitable molecular approaches so that no type of mutation is missed: \u201ceach lost mutation means a baby treated improperly\u201d.<\/jats:p>","DOI":"10.3390\/genes11121519","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T04:12:01Z","timestamp":1608523921000},"page":"1519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4610-1216","authenticated-orcid":false,"given":"Nicola","family":"Laforgia","sequence":"first","affiliation":[{"name":"Section of Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Science and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucrezia","family":"De Cosmo","sequence":"additional","affiliation":[{"name":"Section of Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Science and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-3482","authenticated-orcid":false,"given":"Orazio","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlotta","family":"Ranieri","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Sesta","sequence":"additional","affiliation":[{"name":"Neurology Unit, University Hospital Consortium Corporation Polyclinic of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatella","family":"Capodiferro","sequence":"additional","affiliation":[{"name":"Section of Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Science and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9260-8109","authenticated-orcid":false,"given":"Antonino","family":"Pantaleo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7995-2391","authenticated-orcid":false,"given":"Pierluigi","family":"Iapicca","sequence":"additional","affiliation":[{"name":"SOPHiA GENETICS SA HQ, 1025 Saint-Sulpice, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Lastella","sequence":"additional","affiliation":[{"name":"Rare Diseases Centre\u2014Internal Medicine Unit \u201cC. Frugoni\u201d, Polyclinic of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2194-6711","authenticated-orcid":false,"given":"Manuela","family":"Capozza","sequence":"additional","affiliation":[{"name":"Section of Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Science and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Schettini","sequence":"additional","affiliation":[{"name":"Section of Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Science and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9235-8987","authenticated-orcid":false,"given":"Nenad","family":"Bukvic","sequence":"additional","affiliation":[{"name":"Medical Genetics Section, University Hospital Consortium Corporation Polyclinic of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosanna","family":"Bagnulo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Resta","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"},{"name":"Medical Genetics Section, University Hospital Consortium Corporation Polyclinic of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13023-019-1025-5","article-title":"Congenital myasthenic syndromes","volume":"14","author":"Finsterer","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s10072-018-3682-x","article-title":"Italian recommendations for diagnosis and management of congenital myasthenic syndromes","volume":"40","author":"Maggi","year":"2019","journal-title":"Neurol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S1474-4422(14)70201-7","article-title":"Congenital myasthenic syndromes: Pathogenesis, diagnosis, and treatment","volume":"14","author":"Engel","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1590\/0004-282X20160106","article-title":"Clinical and genetic basis of congenital myasthenic syndromes","volume":"74","author":"Batistella","year":"2016","journal-title":"Arq. Neuro-Psiquiatria"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1007\/s00415-014-7520-7","article-title":"Inherited disorders of the neuromuscular junction: An update","volume":"261","author":"Cruz","year":"2014","journal-title":"J. Neurol."},{"key":"ref_6","first-page":"28","article-title":"Congenital myasthenic syndrome: Phenotypic variability in patients harbouring p.T159P mutation in CHRNE gene","volume":"36","author":"Ardissone","year":"2017","journal-title":"Acta Myol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1002\/ajmg.a.36363","article-title":"TBR1 is the candidate gene for intellectual disability in patients with a 2q24.2 interstitial deletion","volume":"164","author":"Palumbo","year":"2014","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Palumbo, O., Palumbo, P., Di Muro, E., Cinque, L., Petracca, A., Carella, M., and Castori, M. (2020). A Private 16q24.2q24.3 Microduplication in a Boy with Intellectual Disability, Speech Delay and Mild Dysmorphic Features. Genes, 11.","DOI":"10.3390\/genes11060707"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ejpn.2004.10.008","article-title":"Clinical variability of CMS-EA (congenital myasthenic syndrome with episodic apnea) due to identical CHAT mutations in two infants","volume":"9","author":"Barisic","year":"2005","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/S0960-8966(01)00336-4","article-title":"Congenital myasthenic syndrome associated with episodic apnea and sudden infant death","volume":"12","author":"Byring","year":"2002","journal-title":"Neuromuscul. Disord."},{"key":"ref_11","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Mefford, H.C., Stephens, K., Amemiya, A., and Ledbetter, N. (2016). Congenital Myasthenic Syndromes, University of Washington. GeneReviews."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s00439-013-1391-3","article-title":"COOH-terminal collagen Q (COLQ) mutants causing human deficiency of endplate acetylcholinesterase impair the interaction of ColQ with proteins of the basal lamina","volume":"133","author":"Arredondo","year":"2014","journal-title":"Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1093\/brain\/116.3.633","article-title":"Congenital endplate acetylcholinesterase deficiency","volume":"116","author":"Hutchinson","year":"1993","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1212\/WNL.0000000000001396","article-title":"Two cases of congenital myasthenic syndrome with vocal cord paralysis","volume":"84","author":"Brady","year":"2015","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9654","DOI":"10.1073\/pnas.95.16.9654","article-title":"Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme","volume":"95","author":"Ohno","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e117","DOI":"10.1212\/NXG.0000000000000117","article-title":"Copy number analysis reveals a novel multiexon deletion of the COLQ gene in congenital myasthenia","volume":"2","author":"Wang","year":"2016","journal-title":"Neurol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0035-3787(04)70887-5","article-title":"Congenital myasthenic syndromes phenotypic expression and pathophysiological characterisation","volume":"160","author":"Andreux","year":"2004","journal-title":"Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1097\/CND.0000000000000160","article-title":"COLQ-Related Congenital Myasthenic Syndrome and Response to Salbutamol Therapy","volume":"18","author":"Padmanabha","year":"2017","journal-title":"J. Clin. Neuromuscul. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s00415-011-6204-9","article-title":"A retrospective clinical study of the treatment of slow-channel congenital myasthenic syndrome","volume":"259","author":"Chaouch","year":"2012","journal-title":"J. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1136\/jmg.2008.063693","article-title":"Mutations in LAMB2 causing a severe form of synaptic congenital myasthenic syndrome","volume":"46","author":"Maselli","year":"2009","journal-title":"J. Med Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/12\/1519\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:47:00Z","timestamp":1760179620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/12\/1519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,18]]},"references-count":20,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["genes11121519"],"URL":"https:\/\/doi.org\/10.3390\/genes11121519","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2020,12,18]]}}}