Microphthalmia with linear skin defects syndrome (MLS): a male with a mosaic paracentric inversion of XpKutsche K.a · Werner W.b · Bartsch O.b · von der Wense A.c · Meinecke P.d · Gal A.a
aInstitut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Hamburg; bInstitut für Klinische Genetik, Medizinische Fakultät der Technischen Universität Dresden, Dresden; cAbteilung für Neonatologie und pädiatrische Intensivmedizin, dAbteilung für Medizinische Genetik, Altonaer Kinderkrankenhaus, Hamburg (Germany)
The microphthalmia with linear skin defects syndrome (MLS) is an X-linked dominant disorder with male lethality. In the majority of the patients reported, the MLS syndrome is caused by segmental monosomy of the Xp22.3 region. To date, five male patients with MLS and 46,XX karyotype (“XX males”) have been described. Here we report on the first male case with MLS and an XY complement. The patient showed agenesis of the corpus callosum, histiocytoid cardiomyopathy, and lactic acidosis but no microphthalmia, and carried a mosaic subtle inversion of the short arm of the X chromosome in 15% of his peripheral blood lymphocytes, 46,Y,inv(X)(p22.13∼22.2p22.32∼22.33)/46,XY. By fluorescence in situ hybridization (FISH), we showed that YAC 225H10 spans the breakpoint in Xp22.3. End-sequencing and database analysis revealed a YAC insert of at least 416 kb containing the genes HCCS and AMELX, and exons 2–16 of ARHGAP6. Molecular cytogenetic data suggest that the Xp22.3 inversion breakpoint is located in intron 1 of ARHGAP6, the gene encoding the Rho GTPase activating protein 6. Future molecular studies in karyotypically normal female MLS patients to detect submicroscopic rearrangements including the ARHGAP6 gene as well as mutation screening of ARHGAP6 in patients with no obvious chromosomal rearrangements will clarify the role of this gene in MLS syndrome.
© 2002 S. Karger AG, Basel
W.W. and O.B. contributed equally to this work.
Request reprints from Kerstin Kutsche, PhD, Institut für Humangenetik
Universitätsklinikum Hamburg-Eppendorf, Butenfeld 42
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Supported by a grant from the Foundation Fighting Blindness (USA).
Received 30 October 2002;
manuscript accepted 20 December 2002.
Number of Print Pages : 6
Number of Figures : 2, Number of Tables : 0, Number of References : 53
Cytogenetic and Genome Research
Formerly ‘Cytogenetics and Cell Genetics’
Vol. 99, No. 1-4, Year 2002 (Cover Date: 2002)
Journal Editor: H.P. Klinger, Bronx, N.Y.; M. Schmid, Würzburg
ISSN: 1424–8581 (print), 1424–859X (Online)
For additional information: http://www.karger.com/journals/cgr