Microphthalmia with linear skin defects (MLS) syndrome: Clinical, cytogenetic, and molecular characterization of 11 cases

Manuela Morleo, Tiziano Pramparo, Lucia Perone, Giuliana Gregato, Cedric Le Caignec, Robert F. Mueller, Tsutomu Ogata, Annick Raas-Rothschild, Marie Christine De Blois, Louise C. Wilson, Gerald Zaidman, Orsetta Zuffardi, Andrea Ballabio, Brunella Franco

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)190-198
Number of pages9
JournalAmerican Journal of Medical Genetics
Volume137 A
Issue number2
Publication statusPublished - Aug 30 2005


  • Male lethal
  • MLS
  • X-linked dominant
  • Xp22

ASJC Scopus subject areas

  • Genetics(clinical)


Dive into the research topics of 'Microphthalmia with linear skin defects (MLS) syndrome: Clinical, cytogenetic, and molecular characterization of 11 cases'. Together they form a unique fingerprint.

Cite this