Background: The protein O-mannosyltransferase 1, encoded by the POMT1 gene, is a key enzyme in the glycosylation of α-dystroglycan. POMT1-related disorders belong to the group of dystroglycanopathies characterized by a proximally pronounced muscular dystrophy with structural or functional involvement of the brain and/or the eyes. The phenotypic spectrum ranges from the severe Walker-Warburg syndrome (WWS) to milder forms of limb girdle muscular dystrophy (LGMD).
View Article and Find Full Text PDFHoloprosencephaly (HPE) has been defined as a distinct clinical entity with characteristic facial gestalt, which may-or may not-be associated with the true brain malformation observed postmortem in autopsy or in pre- or postnatal imaging. Affected families mainly show autosomal dominant inheritance with markedly reduced penetrance and extremely broad clinical variability even between mutation carriers within the same families. We here present advances in prenatal imaging over the last years, increasing the proportion of individuals with HPE identified prenatally including milder HPE forms and more frequently allowing to detect more severe forms already in early gestation.
View Article and Find Full Text PDFDeletions and duplications of genomic DNA contribute to evolution, phenotypic diversity, and human disease. The underlying mechanisms are incompletely understood. We identified deletions of exon 10 of the SPAST gene in two unrelated families with hereditary spastic paraplegia.
View Article and Find Full Text PDFThe discovery of copy number variations (CNV) in the human genome opened new perspectives in the study of the genetic causes of inherited disorders and the etiology of common diseases. Differently patterned instances of somatic mosaicism in CNV regions have been shown to be present in monozygotic twins and throughout different tissues within an individual. A single-cell-level investigation of CNV in different human cell types led us to uncover mitotically derived genomic mosaicism, which is stable in different cell types of one individual.
View Article and Find Full Text PDFWith the progress of array technologies and the enabled screening of individual human genomes, a new kind of polymorphism has been described - the so-called copy number variation (CNV) polymorphism. Copy number variants can be found in around 12% of the human genome sequence and have a size of up to several hundred kilobase pairs. These variants can not only differ between individuals, but also between corresponding alleles on homologous chromosomes.
View Article and Find Full Text PDFMolecular cytogenetics and especially fluorescence in situ hybridization (FISH) banding approaches are nowadays standard for the exact characterization of simple, complex, and cryptic chromosomal aberrations within the human genome. FISH-banding techniques are any kind of FISH techniques, which provide the possibility to characterize simultaneously several chromosomal subregions smaller than a chromosome arm. FISH banding methods fitting that definition may have quite different characteristics, but share the ability to produce a DNA-specific chromosomal banding.
View Article and Find Full Text PDFThe discovery of copy number variations (CNV) in the human genome opened new perspectives on the study of the genetic causes of inherited disorders and the aetiology of common diseases. Here, a single-cell-level investigation of CNV in different human tissues led us to uncover the phenomenon of mitotically derived genomic mosaicism, which is stable in different cell types of one individual. The CNV mosaic ratios were different between the 10 individuals studied.
View Article and Find Full Text PDFThe fusion gene BCR/ABL arises in connection with a complex translocation event in 2-10% of cases with chronic myeloid leukemia (CML). Due to causative treatment with Imatinib most cases with variant rearrangements show no specific prognostic significance, though the events of therapy resistance remain to be studied. Herein we report on three CML cases with complex chromosomal aberrations not observed before, involving chromosomal regions such as 1p32, 2q11 and 6q12.
View Article and Find Full Text PDFMajor neurological disorders may accompany rare chromosomal abnormalities. As an example of this rare condition, we present a case with microcephaly, mental retardation, developmental delay, hyperactivity, stereotypic movements, seizures and dysmorphic facial appearance in whom a mosaic ring chromosome 18 was found [45,XX,-18/46,XX,r(18)/46,XX,dicr(18)]. Although ring chromosome 18 phenotype has been known for a long time, this is the third reported patient with a dicentric ring chromosome 18 mosaicism.
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