title: Microphthalmia with linear skin defects (MLS) syndrome: clinical, cytogenetic, and molecular characterization of 11 cases.
abstract: The microphthalmia with linear skin defects (MLS) syndrome (MIM 309801) is a severe and rare developmental disorder, which is inherited as an X-linked dominant trait with male lethality. In the vast majority of patients, this syndrome is associated with terminal deletion of the Xp22.3 region. Thirty-five cases have been described to date in the literature since the first description of the syndrome in the early 1990s. We now report on the clinical, cytogenetic, and molecular characterization of 11 patients, 7 of whom have not been described previously. Seven of these patients have chromosomal abnormalities of the short arm of the X-chromosome, which were characterized and defined by fluorescence in situ hybridization (FISH) analysis. Intriguingly, one of the patients displays an interstitial Xp22.3 deletion, which to the best of our knowledge is the first reported for this condition. Finally we report on the identification and molecular characterization of four cases with clinical features of MLS but apparently normal karyotypes, verified by FISH analysis using genomic clones spanning the MLS minimal critical region, and with genome-wide analysis using a 1 Mb resolution BAC microarray. These patients made it possible to undertake mutation screening of candidate genes and may prove critical for the identification of the gene responsible for this challenging and intriguing genetic disease.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Morleo
authors.forename: Tiziano
authors.initials: T
authors.lastname: Pramparo
authors.forename: Lucia
authors.initials: L
authors.lastname: Perone
authors.forename: Giuliana
authors.initials: G
authors.lastname: Gregato
authors.forename: Cedric
authors.initials: C
authors.lastname: Le Caignec
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mueller
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Annick
authors.initials: A
authors.lastname: Raas-Rothschild
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: de Blois
authors.forename: Louise C
authors.initials: LC
authors.lastname: Wilson
authors.forename: Gerald
authors.initials: G
authors.lastname: Zaidman
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
authors.forename: Andrea
authors.initials: A
authors.lastname: Ballabio
authors.forename: Brunella
authors.initials: B
authors.lastname: Franco
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D002648:Child; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D008850:Microphthalmos / Q000473:pathology*; D020161:Physical Chromosome Mapping / Q000379:methods; D012868:Skin Abnormalities; D013577:Syndrome