{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:58:53Z","timestamp":1761897533586,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"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>X-linked adrenoleukodystrophy (X-ALD, OMIM #300100) is the most common peroxisomal disorder clinically characterized by two main phenotypes: adrenomyeloneuropathy (AMN) and the cerebral demyelinating form of X-ALD (cerebral ALD). The disease is caused by defects in the gene for the adenosine triphosphate (ATP)-binding cassette protein, subfamily D (ABCD1) that encodes the peroxisomal transporter of very-long-chain fatty acids (VLCFAs). The defective function of ABCD1 protein prevents \u03b2-oxidation of VLCFAs, which thus accumulate in tissues and plasma, to represent the hallmark of the disease. As in many X-linked diseases, it has been routinely expected that female carriers are asymptomatic. Nonetheless, recent findings indicate that most ABCD1 female carriers become symptomatic, with a motor disability that typically appears between the fourth and fifth decade. In this paper, we report a large family in which affected males died during the first decade, while affected females develop, during the fourth decade, progressive lower limb weakness with spastic or ataxic-spastic gait, tetra-hyperreflexia with sensory alterations. Clinical and genetic evaluations were performed in nine subjects, eight females (five affected and three healthy) and one healthy male. All affected females were carriers of the c.1661G&gt;A (p.Arg554His, rs201568579) mutation. This study strengthens the relevance of clinical symptoms in female carriers of ABCD1 mutations, which leads to a better understanding of the role of the genetic background and the genotype-phenotype correlation. This indicates the relevance to include ABCD1 genes in genetic panels for gait disturbance in women.<\/jats:p>","DOI":"10.3390\/genes12050775","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T12:58:07Z","timestamp":1621429087000},"page":"775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Large Family with p.Arg554His Mutation in ABCD1: Clinical Features and Genotype\/Phenotype Correlation in Female Carriers"],"prefix":"10.3390","volume":"12","author":[{"given":"Rosa","family":"Campopiano","sequence":"first","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Femiano","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Antonietta","family":"Chiaravalloti","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-0309","authenticated-orcid":false,"given":"Rosangela","family":"Ferese","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Centonze","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Laboratory of Synaptic Immunopathology, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Buttari","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Zampatti","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Genomic Medicine Laboratory, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirco","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino \u201cCarlo Bo\u201d, 61029 Urbino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Amatori","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino \u201cCarlo Bo\u201d, 61029 Urbino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmelo","family":"D\u2019Alessio","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emiliano","family":"Giardina","sequence":"additional","affiliation":[{"name":"Genomic Medicine Laboratory, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"},{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-5084","authenticated-orcid":false,"given":"Francesco","family":"Fornai","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Biagioni","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Storto","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Gambardella","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Department of Biomolecular Sciences, University of Urbino \u201cCarlo Bo\u201d, 61029 Urbino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/ncpneuro0421","article-title":"X-linked adrenoleukodystrophy","volume":"3","author":"Moser","year":"2007","journal-title":"Nat. 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