{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:36:39Z","timestamp":1747182999458,"version":"3.40.5"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pathogenic variants in the <jats:italic>AP4B1<\/jats:italic> gene lead to a rare form of hereditary spastic paraplegia (HSP) known as SPG47. We report on a patient with a clinical suspicion of complicated HSP of the lower limbs with intellectual disability, as well as a novel homozygous noncanonical splice site variant in the <jats:italic>AP4B1<\/jats:italic> gene, in which the effect on splicing was validated by RNA analysis.<\/jats:p><jats:p>We sequenced 152 genes associated with HSP using Next\u2010Generation Sequencing (NGS). We isolated total RNA from peripheral blood and generated cDNA using reverse transcription\u2010polymerase chain reaction (RT\u2010PCR). A region of <jats:italic>AP4B1<\/jats:italic> mRNA was amplified by PCR and the fragments obtained were purified from the agarose gel and sequenced.<\/jats:p><jats:p>We found a homozygous variant of uncertain significance in the <jats:italic>AP4B1<\/jats:italic> gene NM_006594.4: c.1511\u20106C&gt;G in the proband. Two different <jats:italic>AP4B1<\/jats:italic> mRNA fragments were obtained in the patient and his carrier parents. The shorter fragment was the predominant fragment in the patient and revealed a deletion with skipping of the <jats:italic>AP4B1<\/jats:italic> exon 10. The patient's longer fragment corresponded to an insertion of the last five nucleotides of <jats:italic>AP4B1<\/jats:italic> intron 9. We confirmed that this variant affects the normal splicing of RNA, sustaining the molecular diagnosis of SPG47 in the patient.<\/jats:p>","DOI":"10.1111\/ahg.12455","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T11:48:42Z","timestamp":1640000922000},"page":"109-118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hereditary spastic paraplegia associated with a novel homozygous intronic noncanonical splice site variant in the <i>AP4B1<\/i> gene"],"prefix":"10.1111","volume":"86","author":[{"given":"Clara","family":"G\u00f3mez\u2010Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, INGEMM La Paz University Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Pizarro\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, INGEMM La Paz University Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Rodr\u00edguez\u2010Antol\u00edn","sequence":"additional","affiliation":[{"name":"Cancer Epigenetics Laboratory, INGEMM La Paz University Hospital  Madrid Spain"},{"name":"Biomarkers and Experimental Therapeutics in Cancer, IdiPAZ  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Pascual\u2010Pascual","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology La Paz University Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar","family":"Garcia\u2010Romero","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology La Paz University Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Rodriguez\u2010Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Next 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Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4438-8900","authenticated-orcid":false,"given":"Rosa J","family":"Torres","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory La Paz University Hospital Health Research Institute (FIBHULP), IdiPAZ  Madrid Spain"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII  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