Parallel deletion and duplication at 7q11.23 in a silent carrier for two reciprocal syndromic disorders.

Partial deletions at chromosome 7q11.23 are causative for the autosomal-dominant Williams-Beuren syndrome (WBS), whereas the partial duplication of this region leads to the 7q11.23 duplication syndrome.

Is Fetal Hydrops in Turner Syndrome a Risk Factor for the Development of Maternal Mirror Syndrome?

Mirror syndrome is a rare and serious maternal condition associated with immune and non-immune fetal hydrops after 16 weeks of gestational age. Subjacent conditions associated with fetal hydrops may carry different risks for Mirror syndrome. Fetuses with Turner syndrome are frequently found to be hydropic on ultrasound.

The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice.

Polygenic risk score analyses on embryos (PGT-P) are being marketed by some private testing companies to parents using in vitro fertilisation as being useful in selecting the embryos that carry the least risk of disease in later life. It appears that at least one child has been born after such a procedure. But the utility of a PRS in this respect is severely limited, and to date, no clinical research has been performed to assess its diagnostic effectiveness in embryos.

Bi-allelic loss-of-function variants in cause severe fetal akinesia with arthrogryposis multiplex.

Background: Fetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear in many individuals. We aimed to further define the set of genes involved.

Opportunistic genomic screening. Recommendations of the European Society of Human Genetics.

If genome sequencing is performed in health care, in theory the opportunity arises to take a further look at the data: opportunistic genomic screening (OGS). The European Society of Human Genetics (ESHG) in 2013 recommended that genome analysis should be restricted to the original health problem at least for the time being. Other organizations have argued that 'actionable' genetic variants should or could be reported (including American College of Medical Genetics and Genomics, French Society of Predictive and Personalized Medicine, Genomics England).

Web-based return of BRCA2 research results: one-year genetic counselling experience in Iceland.

There is an increased pressure to return results from research studies. In Iceland, deCODE Genetics has emphasised the importance of returning results to research participants, particularly the founder pathogenic BRCA2 variant; NM_000059.3:c.

Hereditary hyperferritinaemia-cataract syndrome (HHCS) - an underestimated condition: ferritin light chain variant spectrum in German families.

Background In hereditary hyperferritinaemia-cataract syndrome (HHCS), single nucleic acid alterations in the ferritin light chain (L-ferritin) iron response element (IRE) constitutively derepress ferritin synthesis, resulting in hyperferritinaemia, L-ferritin deposits in the lens of the eye and early bilateral cataract onset. Methods In this study, six German families with putative HHCS were analysed. Clinical diagnosis of HHCS was based on medical history, evaluation of ferritin serum levels, transferrin saturation and clinical ophthalmological examination.

Cortisol, cortisone, and BDNF in amniotic fluid in the second trimester of pregnancy: Effect of early life and current maternal stress and socioeconomic status.

The prenatal environment shapes the offspring's phenotype; moreover, transgenerational stress and stress during pregnancy may play a role. Brain-derived neurotrophic factor (BDNF) and glucocorticoids influence neurodevelopment during pregnancy, and there is evidence that BDNF in amniotic fluid is mainly of fetal origin, while the source of glucocorticoids is maternal. We tested the hypothesis that maternal early life stress, psychiatric diagnoses, anxiety, perceived stress, and socioeconomic status influence BDNF and glucocorticoid concentrations in amniotic fluid in the second trimester.

Familial aortic disease and a large duplication in chromosome 16p13.1.

Background And Purpose: A recurrent duplication of chromosome 16p13.1 was associated with aortic dissection as well as with cervical artery dissection. We explore the segregation of this duplication in a family with familial aortic disease.

A 15q24 microdeletion in transient myeloproliferative disease (TMD) and acute megakaryoblastic leukaemia (AMKL) implicates PML and SUMO3 in the leukaemogenesis of TMD/AMKL.

Transient myeloproliferative disorder (TMD) of the newborn and acute megakaryoblastic leukaemia (AMKL) in children with Down syndrome (DS) represent paradigmatic models of leukaemogenesis. Chromosome 21 gene dosage effects and truncating mutations of the X-chromosomal transcription factor GATA1 synergize to trigger TMD and AMKL in most patients. Here, we report the occurrence of TMD, which spontaneously remitted and later progressed to AMKL in a patient without DS but with a distinct dysmorphic syndrome.

Spatial and kinematic features of apraxic movement depend on the mode of execution.

Knowledge about the dependency of apraxic movements on the mode of execution may enhance the understanding of apraxia and of the cerebral representation of actions. We examined a common tool-use action in nine patients with left hemisphere damage and apraxia. Arm movements during the use of a handsaw were measured and tested in three different modes of execution: pantomime, pantomime with a bar shaped like the handle of the saw, and actual sawing.

The effect of tactile feedback on pantomime of tool use in apraxia.

Objective: To investigate whether apraxic patients' better performance with real tools compared to miming is due to the tactile feedback provided by holding the tool.

Methods: Ten patients with aphasia and apraxia from left hemisphere damage were asked to demonstrate the use of 12 tools and objects under three conditions: miming with empty hands, miming with an implement shaped like the handle of the tool, and using the real tool with its corresponding object.

Results: Whereas real tool use was much better than pantomime in all patients, tactile feedback from the isolated handle facilitated miming only in some and deteriorated it in others so that across the group there was no significant improvement.

Severe form of thyroid hormone resistance in a patient with homozygous/hemizygous mutation of T3 receptor gene.

Resistance to thyroid hormone syndrome (RTH) is a rare disorder, usually inherited as an autosomal dominant trait. Patients with RTH are usually euthyroid but can occasionally present with signs and symptoms of thyrotoxicosis or rarely with hypothyroidism. Affected individuals are usually heterozygous for mutations in the thyroid hormone receptor beta gene (TR-beta).

Relationships and distinctions in iron-regulatory networks responding to interrelated signals.

Specialized cDNA-based microarrays (IronChips) were developed to investigate complex physiological gene-regulatory patterns in iron metabolism. Approximately 115 human cDNAs were strategically selected to represent genes involved either in iron metabolism or in interlinked pathways (eg, oxidative stress, nitric oxide [NO] metabolism, or copper metabolism), and were immobilized on glass slides. HeLa cells were treated with iron donors or iron chelators, or were subjected to oxidative stress (H(2)O(2)) or NO (sodium nitroprusside).

Comparison of fluorescent tag DNA labeling methods used for expression analysis by DNA microarrays.

Gene expression profiling by DNA microarrays has found wide application in many fields of biomedical research. The protocols for this technique are not yet standardized, and for each given step in microarray analysis a number of different protocols are in use. As a consequence, results obtained in different laboratories can be difficult to compare.

Ellis-van Creveld syndrome: a generalized dysplasia of enchondral ossification.

We report a 25-week fetus with lethal Ellis-van Creveld syndrome who was diagnosed prenatally from the US detection of a narrow chest, postaxial polydactyly of the hands, short acro-/mesomelic limbs and a ventricular septal defect. The postnatal radiographic features of the skeleton confirmed the diagnosis. Literature review of the histopathology of the physeal growth plate is contradictory, varying between retardation of the hypertrophic chondrocytes without disorganization and marked disorganization of the proliferating chondrocytes.

Short-rib-polydactyly syndrome type Verma-Naumoff-Le Marec in a fetus with histological hallmarks of type Saldino-Noonan but lacking internal organ abnormalities.

Up to seven short-rib-polydactyly (SRP) syndromes have been identified so far with marked clinical and pathological overlap. We describe a 32-week-old, nonhydropic male fetus with thoracic "dysplasia," short limbs, and unilateral postaxial polydactyly. All internal organs were normally developed, including the central nervous system.

Telencephalosynapsis (synencephaly) and rhombencephalosynapsis with posterior fossa ventriculocele ('Dandy-Walker cyst'): an unusual aberrant syngenetic complex.

Agenesis of the cerebellar vermis (paleocerebellar agenesis) with fusion of the cerebellar hemispheres (rhombencephalosynapsis) is a rare malformation of the central nervous system (CNS). Its combination with synencephaly (telencephalosynapsis), telencephalic ventricular aplasia, aqueductal atresia and cystic fourth ventricle has not yet been described, as far as we know. Here, we report this combination in a 23-weeks' gestation male fetus who was aborted to a 24-year-old diabetic mother.

Comparative evaluation of diepoxybutane sensitivity and cell cycle blockage in the diagnosis of Fanconi anemia.

Fanconi anemia (FA) is a clinically and genetically heterogenous disease that is usually diagnosed on the basis of chromosomal instability reflecting the hypersensitivity towards the DNA cross-linking agents diepoxybutane (DEB) and/or mitomycin C. A less well-known cellular feature that characterizes FA patients is an intrinsic cell cycle disturbance consisting of prolonged progression through, and arrest within, the G2 phase compartment of the cell cycle. In a collaborative blind study, we have evaluated 72-hour lymphocyte cultures from 66 patients with clinical suspicion of FA both for DEB sensitivity and cell cycle disturbance.