title: A New Splicing Mutation in the L1CAM Gene Responsible for X-Linked Hydrocephalus (HSAS).
abstract: X-linked hydrocephalus (XLH) is a genetic disorder leading to a syndrome characterized by mental retardation, bilateral adducted thumbs, and spasticity of upper and lower limbs. In most cases, X-linked mutation leads to a defective activity of the neuronal cell adhesion molecule L1CAM (L1 cell adhesion molecule, OMIM 308840). Depending on mutations of L1CAM, four X-linked neurological syndromes have been described. These syndromes are very different albeit each one possesses marked variability. In the present study, we describe a novel L1CAM mutation in a 33-year-old woman reporting two voluntary terminations of pregnancy due to fetal hydrocephalus. The genetic analysis identified the potential splicing variant c.1267+5delG. When analyzed in vitro, this mutation produces the skipping of exon 10. The same mutation was confirmed in analyzing DNA from amniocytes from the second pregnancy, and ultrasound scan and autopsy confirmed the occurrence of a severe L1 syndrome. These data describe a novel L1 mutation which improves our understanding on genotype-phenotype correlation while confirming the importance of prenatal screening for L1CAM mutations.
authors.affiliation: IRCCS Neuromed, Localita' Camerelle, 86077, Pozzilli, Italy. ferese.rosangela@gmail.com.
authors.forename: Rosangela
authors.initials: R
authors.lastname: Ferese
authors.affiliation: IRCCS Neuromed, Localita' Camerelle, 86077, Pozzilli, Italy.|Molecular Genetics Laboratory UILDM, Santa Lucia Foundation, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Zampatti
authors.affiliation: IRCCS Neuromed, Localita' Camerelle, 86077, Pozzilli, Italy.
authors.forename: Anna Maria Pia
authors.initials: AM
authors.lastname: Griguoli
authors.affiliation: IRCCS Neuromed, Localita' Camerelle, 86077, Pozzilli, Italy.|Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fornai
authors.affiliation: Molecular Genetics Laboratory UILDM, Santa Lucia Foundation, Rome, Italy.|Department of Biomedicine and Prevention, School of Medicine, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giardina
authors.affiliation: San Pietro Fatebenefratelli Hospital, UOSD Medical Genetics, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Barrano
authors.affiliation: IRCCS Neuromed, Localita' Camerelle, 86077, Pozzilli, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Albano
authors.affiliation: IRCCS Neuromed, Localita' Camerelle, 86077, Pozzilli, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Campopiano
authors.affiliation: IRCCS Neuromed, Localita' Camerelle, 86077, Pozzilli, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Scala
authors.affiliation: IRCCS Neuromed, Localita' Camerelle, 86077, Pozzilli, Italy.|Department of Biomedicine and Prevention, School of Medicine, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.affiliation: IRCCS Neuromed, Localita' Camerelle, 86077, Pozzilli, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gambardella
mesh_terms: D000328:Adult; D005091:Exons; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D006849:Hydrocephalus / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012326:RNA Splicing
chemical_list: D039842:Neural Cell Adhesion Molecule L1
keywords: L1 syndrome; L1CAM; Minigene assay; X-linked hydrocephalus