Xp Microdeletion Syndrome Characterized by Pathognomonic Linear Skin Defects on the Head and Neck

Paulger, Brent R.; Kraus, Eric W.; Pulitzer, Donald R.; Moore, Charleen M.

doi:10.1111/j.1525-1470.1997.tb00422.x

Cited by 21 publications

(26 citation statements)

References 15 publications

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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%

“…Remarkably, four female patients with an apparently normal karyotype have also been described (Happle et al, 1993;Bird et al, 1994;Cox et al, 1998;Zvulunov et al, 1998) suggesting that submicroscopic rearrangements or "short length" mutations in a yet unidentified gene may also be responsible for the trait. To date, three affected males and twin brothers have been reported, all with an XX complement and a translocation between Xp and Yp (Lindsay et al, 1994;Paulger et al, 1997;Stratton et al, 1998;Kono et al, 1999;Anguiano et al, 2003). A sixth patient had ambiguous genitalia and a 46,XX karyotype (Camacho et al, 1997).…”

confidence: 99%

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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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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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“…Zvulunov et al [1998] described peculiar ultrastructural ®ndings (cytoplasmic bodies within keratocytes). Recent studies have reported smooth muscle hamartomata, rather than the presumed dermal aplasia [Paulger et al, 1997;Stratton et al, 1998]. Hypoplasia or agenesis of the corpus callosum is frequently reported in the syndrome [for reviews of reported cases, see Bird et al, 1994].…”

Section: Introductionmentioning

confidence: 99%

Corpus callosum agenesis, multiple cysts, skin defects, and subtle ocular abnormalities with a de novo mutation [45,XX,der(5), t(5;14) (pter;q11.2)]

Zannolli¹,

Mostardini²,

Pucci³

et al. 2001

Am. J. Med. Genet.

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We report on a 2-year-old girl with a de novo mutation [45,XX,der(5),t(5;14) (pter;q11.2)] with corpus callosum agenesis, multiple cysts (cerebral and cardiac), subtle eye abnormalities, and at least two different skin defects, strongly indicating neuroectodermal involvement, as a neuromuscular choristoma (hamartoma) and an eccrine hamartoma. Fluorescent in situ hybridization with different single-locus probes showed that chromosome 5 has a very small deletion, confined to a region composed of repetitive sequences. By contrast, the long (q) arm of chromosome 14 seems to be much more involved in the rearrangement, with partial monosomy spanning from the centromere to the D14S72 and D14S261 loci. The extent of the deleted region of chromosome 14 is approximately 16 cM. To our knowledge, this is the smallest reported deletion involving the chromosome 14q11.2 region to be associated with a developmental disorder resulting in variable eye, skin, and brain anomalies. We suggest that a new syndrome, mimicking in some ways the MLS phenotype, is caused by a deletion in the chromosome 14q11.2 region.

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“…A few individuals had developmental delay, short stature and facial dysmorphism (Table 1). Rarely, hearing loss and anal atresia with ectopic anus and fistula, as seen in patient 5 have also been observed in other cases [13,35,40,41]. Patient 2 and one reported girl [4] carried the HCCS nonsense mutation c.589C > T (p.R197*).…”

Section: Discussionmentioning

confidence: 58%

Clinical spectrum of females with HCCS mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects (MLS) syndrome

Rahden

Rau

Fuchs

et al. 2014

Orphanet J Rare Dis

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BackgroundSegmental Xp22.2 monosomy or a heterozygous HCCS mutation is associated with the microphthalmia with linear skin defects (MLS) or MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome, an X-linked disorder with male lethality. HCCS encodes the holocytochrome c-type synthase involved in mitochondrial oxidative phosphorylation (OXPHOS) and programmed cell death.MethodsWe characterized the X-chromosomal abnormality encompassing HCCS or an intragenic mutation in this gene in six new female patients with an MLS phenotype by cytogenetic analysis, fluorescence in situ hybridization, sequencing, and quantitative real-time PCR. The X chromosome inactivation (XCI) pattern was determined and clinical data of the patients were reviewed.ResultsTwo terminal Xp deletions of ≥11.2 Mb, two submicroscopic copy number losses, one of ~850 kb and one of ≥3 Mb, all covering HCCS, 1 nonsense, and one mosaic 2-bp deletion in HCCS are reported. All females had a completely (>98:2) or slightly skewed (82:18) XCI pattern. The most consistent clinical features were microphthalmia/anophthalmia and sclerocornea/corneal opacity in all patients and congenital linear skin defects in 4/6. Additional manifestations included various ocular anomalies, cardiac defects, brain imaging abnormalities, microcephaly, postnatal growth retardation, and facial dysmorphism. However, no obvious clinical sign was observed in three female carriers who were relatives of one patient.ConclusionOur findings showed a wide phenotypic spectrum ranging from asymptomatic females with an HCCS mutation to patients with a neonatal lethal MLS form. Somatic mosaicism and the different ability of embryonic cells to cope with an OXPHOS defect and/or enhanced cell death upon HCCS deficiency likely underlie the great variability in phenotypes.

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Xp Microdeletion Syndrome Characterized by Pathognomonic Linear Skin Defects on the Head and Neck

Cited by 21 publications

References 15 publications

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

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

Corpus callosum agenesis, multiple cysts, skin defects, and subtle ocular abnormalities with a de novo mutation [45,XX,der(5), t(5;14) (pter;q11.2)]

Clinical spectrum of females with HCCS mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects (MLS) syndrome

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