{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:53:03Z","timestamp":1790697183869,"version":"4.1.0"},"reference-count":12,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"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":["Birth Defects Research"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neuronal ceroid lipofuscinoses (NCLs) form a clinically and genetically heterogeneous group of inherited neurodegenerative disorders that share common neuropathological features. Although they are the first cause of neurodegenerative disorders in children, their congenital forms are rarely documented. They are classically due to mutations in the <jats:italic>CTSD<\/jats:italic> gene (the CLN10 disease). Affected newborns usually present severe microcephaly, seizures and respiratory failure leading to death within the first postnatal days or weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Cases<\/jats:title><jats:p>We report on two siblings, in which exome sequencing identified a novel homozygous <jats:italic>CTSD<\/jats:italic> variant. The first sib presented at birth with seizures, rapidly progressive postnatal microcephaly and visual deficiency related to retinal dysfunction. Progressive neurological deterioration leads to death at the age of 24\u2009months. Cathepsin D activity was reduced in the cultured fibroblasts of this patient. The second sib, a fetus of 36\u2009weeks of gestation, was delivered after pregnancy termination for brain abnormalities (in accordance with French Legislation) suggesting a recurrence of the disease. Fetal postmortem examination disclosed neuropathological features consistent with NCL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Congenital NCL related to <jats:italic>CTSD<\/jats:italic> mutations is a neuronal storage disorder that produces in the developing brain diffuse neurodegeneration and white matter atrophy resulting in a progressive and rapidly lethal microcephaly.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1950","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T09:29:14Z","timestamp":1631006954000},"page":"1324-1332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Prenatal\u2010onset of congenital neuronal ceroid lipofuscinosis with a novel <scp><i>CTSD<\/i><\/scp> mutation"],"prefix":"10.1002","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2932-5282","authenticated-orcid":false,"given":"Suzanne","family":"Chartier","sequence":"first","affiliation":[{"name":"Unit\u00e9 d'Embryof\u0153topathologie H\u00f4pital Necker\u2010Enfants Malades, AP\u2010HP.Centre  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0767-2822","authenticated-orcid":false,"given":"Lucile","family":"Boutaud","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d'Embryof\u0153topathologie H\u00f4pital Necker\u2010Enfants Malades, AP\u2010HP.Centre  Paris France"},{"name":"Universit\u00e9 de Paris, Imagine Institute, INSERM UMR 1163  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9750-9748","authenticated-orcid":false,"given":"Edouard","family":"Le Guillou","sequence":"additional","affiliation":[{"name":"Service de Biochimie M\u00e9tabolique H\u00f4pital Necker\u2010Enfants Malades, AP\u2010HP.Centre  Paris France"},{"name":"Universit\u00e9 de Paris, Institut Necker Enfants Malades INSERM U1151  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Alby","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Mol\u00e9culaire H\u00f4pital Necker\u2010Enfants Malades, AP\u2010HP.Centre  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7104-8496","authenticated-orcid":false,"given":"Clarisse","family":"Billon","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d'Embryof\u0153topathologie H\u00f4pital Necker\u2010Enfants Malades, AP\u2010HP.Centre  Paris France"},{"name":"D\u00e9partement de G\u00e9n\u00e9tique H\u00f4pital Europ\u00e9en Georges Pompidou, APHP  Paris 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