1/7. Xp22.3 microdeletion in a 19-year-old girl with clinical features of MLS syndrome.We describe a 19-year-old girl who has clinical features of microphthalmia with linear skin defects (MLS) syndrome caused by a microdeletion of Xp22.3. In addition to the classical ocular abnormalities and linear skin defects she has other features not previously described. She was previously reported in this journal in 1990 as poikiloderma congenitale, but her true diagnosis of an Xp22.3 microdeletion was clarified when fluorescent in situ hybridization (FISH) analysis indicated that one of her X chromosomes had a microdeletion including the KAL gene. We describe this patient with an Xp22.3 microdeletion to heighten awareness among dermatologists of this syndrome and to underscore the difficulties in diagnosing MLS syndrome.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/7. Microphthalmia with linear skin defects syndrome (MLS): a male with a mosaic paracentric inversion of Xp.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 approximately 22.2p22.32 approximately 22.33)[49]/46,XY[271]. 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.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/7. Molecular cytogenetic identification and characterization of a de novo supernumerary neocentromeric derivative chromosome 13.We report a young girl with microphthalmia, conductive deafness, aortic isthmus stenosis, laryngomalacia, and laryngeal stenosis carrying a de novo supernumerary neocentromeric derivative chromosome 13. For the precise identification and characterization of the eu- and heterochromatic content of the marker chromosome, straightforward molecular cytogenetic analyses were performed, such as chromosome microdissection, FISH with different probes (e.g. wcp, alphoid centromeric probes, BAC), centromere-specific multicolor FISH (cenM-FISH), and multicolor banding (MCB). The analyses demonstrated that the marker consisted of an inverted duplication (partial tetrasomy) of the distal portion of chromosome 13 that was separated from the endogenous chromosome 13 centromere. Using an all-centromere probe and multicolor cenM-FISH, no alpha-satellite dna hybridization signal was detectable on any portion of the derivative chromosome. The presence of a functional and active neocentromere on the derivative chromosome 13 was confirmed by positive immunofluorescence signals with CENP-C antibodies. BAC-FISH confirmed the cytogenetic localization of the neocentromere in band 13q31.3. Thus the patient had a mosaic conventional karyotype mos 47,XX, inv dup(13)(qter-->q21.3::q21.3-->q31.3-->neo-->q31.3-->qter)[6]/46,XX [49].- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/7. Second 46,XX male with MLS syndrome.We report on a second 46,XX male with microphthalmia with linear skin defects (MLS) syndrome. In addition to microphthalmia and linear skin streaks, he had a secundum ASD, hypospadias with chordee, anal fistula, and agenesis of corpus callosum with colpocephaly. biopsy of a linear streak showed smooth muscle hamartomata rather than the presumed dermal aplasia. Detailed ophthalmologic examination did not show retinal lacunae typical of aicardi syndrome. dna studies with distal Xp specific probes indicated a deletion in one x chromosome and fluorescence in situ hybridization (FISH) studies with X- and Y-specific probes demonstrated the presence of a derivative x chromosome from an X;Y translocation.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/7. A case of microphthalmos with cyst and partial trisomy 22.A 13-day-old girl was referred for evaluation of a right orbital mass. Ophthalmic examinations revealed microphthalmia with cyst in the right eye and microphthalmia in the left eye. She had lowset ears, auricular fistula, micrognathia, and muscular hypotonia. Chromosomal analysis using fluorescence in-situ hybridization (FISH) showed partial trisomy 22. To our knowledge, microphthalmos with cyst associated with partial trisomy 22 has not been described previously in the English literature. Repeated aspiration resulted in a decrease in size of the cyst.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/7. Microphthalmia with linear skin defects syndrome in a mosaic female infant with monosomy for the Xp22 region: molecular analysis of the Xp22 breakpoint and the X-inactivation pattern.This paper describes a female infant with microphthalmia with linear skin defects syndrome (MLS) and monosomy for the Xp22 region. Her clinical features included right microphthalmia and sclerocornea, left corneal opacity, linear red rash and scar-like skin lesion on the nose and cheeks, and absence of the corpus callosum. Cytogenetic studies revealed a 45,X[18]/46,X,r(X)(p22q21) [24]/46,X,del(X)(p22)[58] karyotype. fluorescence in situ hybridization analysis showed that the ring x chromosome was positive for DXZ1 and XIST and negative for the Xp and Xq telomeric regions, whereas the deleted x chromosome was positive for DXZI, XIST, and the Xq telomeric region and negative for the Xp telomeric region. Microsatellite analysis for 19 loci at the X-differential region of Xp22 disclosed monosomy for Xp22 involving the critical region for the MLS gene, with the breakpoint between DXS1053 and DXS418. X-inactivation analysis for the methylation status of the PGK gene indicated the presence of inactive normal X chromosomes. The Xp22 deletion of our patient is the largest in MLS patients with molecularly defined Xp22 monosomy. Nevertheless, the result of X-inactivation analysis implies that the normal X chromosomes in the 46,X,del(X)(p22) cell lineage were more or less subject to X-inactivation, because normal X chromosomes in the 45,X and 46,X,r(X)(p22q21) cell lineages are unlikely to undergo X-inactivation. This supports the notion that functional absence of the MLS gene caused by inactivation of the normal x chromosome plays a pivotal role in the development of MLS in patients with Xp22 monosomy.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/7. Another observation of microphthalmia in an XX male: microphthalmia with linear skin defects syndrome without linear skin lesions.A case of microphthalmia with Xp microdeletion is reported. The patient was a boy who showed bilateral microphthalmia with corneal opacities, hypospadias without evidence of hypogonadism, and a conduction disturbance of the heart (Wenckebach conduction). No skin lesion was discerned. High-resolution chromosome analysis revealed the karyotype of 46,X,del(X)(p22). The phenotype was considered to be microphthalmia with linear skin defects (MLS) syndrome without skin lesions. polymerase chain reaction and fluorescence in-situ hybridization analyses revealed that the chromosome aberration resulted from an X;Y translocation: the presence of pseudoautosomal boundary Y and the sex-determining region of Y was confirmed, while Xp deletion involving the region distal to DXS1129 was ascertained. Thus the chromosome designation using the ISCN 1995 nomenclature is 46,X,der(X),t(X;Y)(p22.13;q11.2). Despite the absence of skin lesions, the Xp deletion of our patient corresponded to those of previously reported typical cases of MLS syndrome. Our observation further supports the current hypothesis that the phenotypic variation of MLS syndrome represents tissue-different X inactivation rather than different genetic effects of two contiguous genes.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |