MIDAS syndrome respectively MLS syndrome: A separate entity rather than a particular lyonization pattern of the gene causing Goltz syndrome

Mücke, J.; Happle, Rudolf; Theile, H

doi:10.1002/ajmg.1320570123

Cited by 30 publications

(20 citation statements)

References 2 publications

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“…For example, skin lesions are limited to the face and neck in MLS syndrome and skeletal abnormalities, such as clefting of hands or feet, and syndactyly are only present in patients with FDH. 8,9 Recently, the underlying genetic defects of FDH and MLS syndrome have been identified. Heterozygous mutations in the HCCS gene (Xp22.2), encoding the mitochondrial holocytochrome c-type synthase are responsible for MLS.…”

Section: Introductionmentioning

confidence: 99%

Goltz–Gorlin (focal dermal hypoplasia) and the microphthalmia with linear skin defects (MLS) syndrome: no evidence of genetic overlap

et al. 2009

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Focal dermal hypoplasia (FDH) is an X-linked developmental disorder with male lethality characterized by patchy dermal hypoplasia, skeletal and dental malformations, and microphthalmia or anophthalmia. Recently, heterozygous loss-of-function mutations in the PORCN gene have been described to cause FDH. FDH shows some clinical overlap with the microphthalmia with linear skin defects (MLS) syndrome, another X-linked male lethal condition, associated with mutations of HCCS in the majority of cases. We performed DNA sequencing of PORCN in 13 female patients with the clinical diagnosis of FDH as well as four female patients with MLS syndrome and no mutation in HCCS. We identified PORCN mutations in all female patients with FDH. Eleven patients seem to have constitutional PORCN alterations in the heterozygous state and two individuals are mosaic for the heterozygous sequence change in PORCN. No PORCN mutation was identified in the MLS-affected patients, providing further evidence that FDH and MLS do not overlap genetically. X chromosome inactivation (XCI) analysis revealed a random or slightly skewed XCI pattern in leukocytes of individuals with intragenic PORCN mutation suggesting that defective PORCN does not lead to selective growth disadvantage, at least in leukocytes. We conclude that the PORCN mutation detection rate is high in individuals with a clear-cut FDH phenotype and somatic mosaicism can be present in a significant proportion of patients with mild or classic FDH.

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Section: Introductionmentioning

confidence: 99%

Goltz–Gorlin (focal dermal hypoplasia) and the microphthalmia with linear skin defects (MLS) syndrome: no evidence of genetic overlap

et al. 2009

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“…Occasional abnormalities include agenesis of the corpus callosum, sclerocornea, chorioretinal abnormalities, infantile seizures, congenital heart defect, and mental retardation. At least 30 patients have been described so far (Friedman et al, 1988;Al-Gazali et al, 1990;Donnenfeld et al, 1990;Temple et al, 1990;Allanson and Richter, 1991;Gericke et al, 1991;Thies et al, 1991;Lindor et al, 1992;Naritomi et al, 1992;Happle et al, 1993;Bird et al, 1994;Eng et al, 1994;Lindsay et al, 1994;McLeod et al, 1994;Mücke et al, 1995;Camacho et al, 1997;Paulger et al, 1997;Cox et al, 1998;Ogata et al, 1998;Stratton et al, 1998;Zvulunov et al, 1998;Kono et al, 1999;Kayserili et al, 2001;Anguiano et al, 2003).…”

confidence: 99%

“…It has been proposed that functional absence of the MLS gene caused by inactivation of the normal X chromosome in patients with Xp22 monosomy may play a critical role in the development of MLS (reviewed in Van den Veyver, 2001). Moreover, variable tissuespecific X-inactivation is likely to account both for the intrafamilial variability and clinical divergence in sporadic cases (Allanson and Richter, 1991;Ballabio and Andria, 1992;Mücke et al, 1995).…”

confidence: 99%

Microphthalmia with linear skin defects syndrome (MLS): a male with a mosaic paracentric inversion of Xp

Kutsche

Werner²,

Bartsch³

et al. 2002

Cytogenet Genome Res

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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)[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.

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“…Approximately 60% are 46,XX; 15% are 46,XY; 25% show various forms of mosaicism, and fewer than 1% show 46,XX/46,XY chimerism [Hasty and Rock, 1996]. Although rare, there have been previous reports of ovotesticular development due to inherited SRY -positive X/Y translocations, associated with a variable sexual phenotype within the same family [Abbas et al, 1993;Mücke et al, 1995;Jakubowski et al, 2000;Sharp et al, 2004].…”

Section: Discussionmentioning

confidence: 99%

Unique Karyotype: mos 46,X,dic(X;Y)(p22.33;p11.32)/ 45,X/45,dic(X;Y)(p22.33;p11.32) in an Egyptian Patient with Ovotesticular Disorder of Sexual Development

Mazen¹,

Kamel²,

Mohamed³

et al. 2013

Sex Dev

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Ovotesticular disorder of sexual development (OT-DSD) is an unusual form of DSD, characterized by the coexistence of testicular and ovarian tissue in the same individual. In this report, we present clinical, cytogenetic and molecular data of an Egyptian patient with ambiguous genitalia and OT-DSD, who had a unique karyotype comprising 3 different cell lines: mos 46,X,dic(X;Y)(p22.33;p11.32)/45,X/ 45,dic(X;Y)(p22.33;p11.32). This mosaic karyotype probably represents 2 different events: abnormal recombination between the X and Y chromosomes during paternal meiosis and postzygotic abnormality in mitotic segregation of the dic(X;Y) chromosome, resulting in a mosaic karyotype. The presence of the sex-determining region Y (SRY) gene explains the development of testicular tissue. On the other hand, other factors, including the presence of a 45,X cell line, partial SRY deletion, X inactivation pattern, and position effect, could be contributed to genital ambiguity. Explanation of the patient's phenotype in relation to the genotype is discussed with a literature review. We conclude that FISH analysis with X- and Y-specific probes and molecular analysis of the SRY gene are highly recommended and allow accurate diagnosis for optimal management of cases with ambiguous genitalia.

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MIDAS syndrome respectively MLS syndrome: A separate entity rather than a particular lyonization pattern of the gene causing Goltz syndrome

Cited by 30 publications

References 2 publications

Goltz–Gorlin (focal dermal hypoplasia) and the microphthalmia with linear skin defects (MLS) syndrome: no evidence of genetic overlap

Goltz–Gorlin (focal dermal hypoplasia) and the microphthalmia with linear skin defects (MLS) syndrome: no evidence of genetic overlap

Microphthalmia with linear skin defects syndrome (MLS): a male with a mosaic paracentric inversion of Xp

Unique Karyotype: mos 46,X,dic(X;Y)(p22.33;p11.32)/ 45,X/45,dic(X;Y)(p22.33;p11.32) in an Egyptian Patient with Ovotesticular Disorder of Sexual Development

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