3.7 Mb tandem microduplication in chromosome 5p13.1-p13.2 associated with developmental delay, macrocephaly, obesity, and lymphedema. Further characterization of the dup(5p13) syndrome.

In a male patient with developmental delay, autistic behaviour, obesity, lymphedema, hypertension, macrocephaly, and facial features of chromosome 5p duplication (trisomy 5p) a 3.7 Mb de novo tandem microduplication of 5p13.1-13.2 (rs4703415-rs261752, i.e., chr5:35.62-39.36 Mb) was identified. This observation contributes to the characterization and dissection of the 5p13 duplication syndrome. The possible role of increased NIPBL gene dosage is discussed

Microdeletion syndrome 16p11.2-p12.2: Clinical and molecular characterization.

The pericentromeric region on 16p appears to be susceptible to chromosomal rearrangements and several patients with rearrangements in this region have been described. We report on a further patient with a microdeletion 16p11.2-p12.2 in the context of described patients with a deletion in the pericentromeric region of 16p. Minor facial anomalies, feeding difficulties, significant delay in speech development, and recurrent ear infections are common symptoms of the microdeletion syndrome 16p11.2-p12.2. All reported patients so far share a common distal breakpoint at 16p12.2 but vary in the proximal breakpoint at 16p11.2. The microdeletion 16p11.2-p12.2 should be distinguished from the approximately 500 kb microdeletion in 16p11.2 which seems to be associated with autism but not with facial manifestations, feeding difficulties, or developmental delay

Polyneuropathy, Scoliosis, Tall Stature, and Oligodontia Represent Novel Features of the interstitial 6p Deletion Phenotype.

no abstrac

Cohen syndrome diagnosis using whole genome arrays.

Background Cohen syndrome is a rare autosomal recessive disorder with a complex phenotype including psychomotor retardation, microcephaly, obesity with slender extremities, joint laxity, progressive chorioretinal dystrophy/myopia, intermittent isolated neutropenia, a cheerful disposition, and characteristic facial features. The COH1 gene, which contains 62 exons, is so far the only gene known to be associated with Cohen syndrome. Point mutations, deletions and duplications have been described in this gene. Oligonucleotide arrays have reached a resolution which allows the detection of intragenic deletions and duplications, especially in large genes such as COH1. Method and results High density oligonucleotide array data from patients with unexplained mental retardation (n=1523) and normal controls (n=1612) were analysed for copy number variation (CNV) changes. Intragenic heterozygous deletions in the COH1 gene were detected in three patients but no such changes were detected in the controls. Subsequent sequencing of the COH1 gene revealed point mutations in the second allele in all three patients analysed. Conclusion Genome-wide CNV screening with high density arrays provides a tool to detect intragenic deletions in the COH1 gene. This report presents an example of how microarrays can be used to identify autosomal recessive syndromes and to extend the phenotypic and mutational spectrum of recessive disorders

Detectie van submicroscopische chromosomale afwijkingen door middel van array-diagnostiek

Chromosomal microarray enables identifying small genomic deletions and duplications that are not routinely seen on karyotyping. Microarray analysis therefore has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children in the Netherlands since 2008. When invasive prenatal diagnosis is indicated, because of ultrasound abnormalities and/or an increased risk for common aneuploidies (trisomy 21, 18 or 13) at first trimester screening, microarray analysis instead of conventional karyotyping will be applied when targeted molecular rapid aneuploidy detection reveals no abnormalities. Microarray analysis provides around 12-15% extra diagnosis in cases of mental retardation and/or structural abnormalities and it can provide 6% extra diagnosis in prenatal samples with a normal karyotype. Besides finding evident causative abnormalities, microarray analysis increases the detection rates of VOUS (variants of unknown significance) that, in particular during a pregnancy, induce emotional burden en counselling difficulties. Furthermore, CNVs that are pathogenic but not related with the phenotype (e.g. deletion of an oncogene) may complicate pretest and posttest counselling as well, since these findings may have health consequences for both patient and family members. Clinicians who request microarray analysis should be aware of these implications. In this paper, two prenatal and four postnatal case reports illustrate the ability to identify more clinically relevant abnormalities, but also limitations and coincidental findings in microarray analysis.</p

Atomic force microscopy-based mechanobiology

Mechanobiology emerges at the crossroads of medicine, biology , biophysics and engineering and describes how the responses of proteins, cells, tissues and organs to mechanical cues contribute to development, differentiation, physiology and disease. The grand challenge in mechanobiology is to quantify how biological systems sense, transduce, respond and apply mechanical signals. Over the past three decades, atomic force microscopy (AFM) has emerged as a key platform enabling the simultaneous morphological and mechanical characterization of living biological systems. In this Review , we survey the basic principles, advantages and limitations of the most common AFM modalities used to map the dynamic mechanical properties of complex biological samples to their morphology. We discuss how mechanical properties can be directly linked to function, which has remained a poorly addressed issue. We outline the potential of combining AFM with complementary techniques, including optical microscopy and spectroscopy of mechanosensitive fluorescent constructs, super- resolution microscopy , the patch clamp technique and the use of microstructured and fluidic devices to characterize the 3D distribution of mechanical responses within biological systems and to track their morphology and functional state