{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T03:34:37Z","timestamp":1768620877021,"version":"3.49.0"},"reference-count":7,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Appl Genetics"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Coenzyme Q5 (<jats:italic>COQ5<\/jats:italic>), a C-methyltransferase, modifies coenzyme Q10 (COQ10) during biosynthesis and interacts with polyA-tail regulating zinc-finger protein ZC3H14 in neural development. Here, we present a fifth patient (a third family) worldwide with neurodevelopmental and physiological symptoms including <jats:italic>COQ10<\/jats:italic> deficiency. Our patient harbors one novel c.681+1G&gt;A and one recurrent p.Gly118Ser variant within <jats:italic>COQ5<\/jats:italic>. The patient\u2019s mRNA profile reveals multiple <jats:italic>COQ5<\/jats:italic> splice-variants. Subsequently, we comprehensively described patient\u2019s clinical features as compared to phenotype and symptoms of other known congenital coenzyme Q5-linked cases. A core spectrum of <jats:italic>COQ5<\/jats:italic>-associated symptoms includes reduced COQ10 levels, intellectual disability, encephalopathy, cerebellar ataxia, cerebellar atrophy speech regression\/dysarthria, short stature, and developmental delays. Our patient additionally displays dysmorphia, microcephaly, and regressive social faculties. These results formally establish causal association of biallelic <jats:italic>COQ5<\/jats:italic> mutation with pathology, outline a core <jats:italic>COQ5<\/jats:italic>-linked phenotype, and identify mRNA mis-splicing as the molecular mechanism underlying all <jats:italic>COQ5<\/jats:italic> variant-linked pathology to date.<\/jats:p>","DOI":"10.1007\/s13353-023-00773-9","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T03:08:05Z","timestamp":1692587285000},"page":"507-514","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Congenital coenzyme Q5-linked pathology: causal genetic association, core phenotype, and molecular mechanism"],"prefix":"10.1007","volume":"64","author":[{"given":"Mateusz","family":"Dawidziuk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Podwysocka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Jurek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Obersztyn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Bekiesinska-Figatowska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicja","family":"Goszczanska-Ciuchta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewelina","family":"Bukowska-Olech","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka Magdalena","family":"Rygiel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothy Lys","family":"Guilbride","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Wiszniewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3672-5834","authenticated-orcid":false,"given":"Pawel","family":"Gawlinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"issue":"9","key":"773_CR1","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.3390\/jcm10091970","volume":"10","author":"IP Hargreaves","year":"2021","unstructured":"Hargreaves IP (2021) Coenzyme Q10 in mitochondrial and lysosomal disorders. J Clin Med. 10(9):1970","journal-title":"J Clin Med."},{"issue":"1","key":"773_CR2","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1002\/humu.23345","volume":"39","author":"MCV Malicdan","year":"2018","unstructured":"Malicdan MCV et al (2018) A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency. Hum Mutat. 39(1):69\u201379","journal-title":"Hum Mutat."},{"issue":"7367","key":"773_CR3","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature10423","volume":"478","author":"H Najmabadi","year":"2011","unstructured":"Najmabadi H et al (2011) Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature. 478(7367):57\u201363","journal-title":"Nature."},{"issue":"11","key":"773_CR4","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1016\/j.bbalip.2014.08.007","volume":"1841","author":"TP Nguyen","year":"2014","unstructured":"Nguyen TP et al (2014) Molecular characterization of the human COQ5 C-methyltransferase in coenzyme Q10 biosynthesis. Biochim Biophys Acta 1841(11):1628\u20131638","journal-title":"Biochim Biophys Acta"},{"key":"773_CR5","unstructured":"Online Mendelian inheritance in man (n.d.) OMIM\u00ae. Johns Hopkins University, Baltimore, MD. MIM Number: PS607426. World Wide Web URL:\u00a0COQ10 in Online Mendelian Inheritance in Man. https:\/\/www.omim.org\/entry\/607426"},{"issue":"30","key":"773_CR6","doi-asserted-by":"publisher","first-page":"12390","DOI":"10.1073\/pnas.1107103108","volume":"108","author":"Pak","year":"2011","unstructured":"Pak et al (2011) Mutation of the conserved polyadenosine RNA binding protein, ZC3H14\/dNab2, impairs neural function in Drosophila and humans. Proc Natl Acad Sci USA 108(30):12390\u201312395","journal-title":"Proc Natl Acad Sci USA"},{"issue":"9","key":"773_CR7","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1016\/j.bbagen.2016.05.005","volume":"1860","author":"HC Yen","year":"2016","unstructured":"Yen HC et al (2016) Disruption of the human COQ5-containing protein complex is associated with diminished coenzyme Q10 levels under two different conditions of mitochondrial energy deficiency. Biochim Biophys Acta. 1860(9):1864\u20131876","journal-title":"Biochim Biophys Acta."}],"container-title":["Journal of Applied Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13353-023-00773-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13353-023-00773-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13353-023-00773-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T01:06:27Z","timestamp":1693011987000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13353-023-00773-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,21]]},"references-count":7,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["773"],"URL":"https:\/\/doi.org\/10.1007\/s13353-023-00773-9","relation":{},"ISSN":["1234-1983","2190-3883"],"issn-type":[{"value":"1234-1983","type":"print"},{"value":"2190-3883","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,21]]},"assertion":[{"value":"29 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study complies with the latest Declaration of Helsinki and was approved by the Ethics Committee of the Institute of Mother and Child in Warsaw.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from the parents.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors affirm that human research participants provided informed consent for publication of the images in Fig. a.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}