Further delineation of Malan syndrome.

Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 previously reported individuals.

Extending the phenotype associated with the CSNK2A1-related Okur-Chung syndrome-A clinical study of 11 individuals.

Variants in the Protein Kinase CK2 alpha subunit, encoding the CSNK2A1 gene, have previously been reported in children with an intellectual disability and dysmorphic facial features syndrome: now termed the Okur-Chung neurodevelopmental syndrome. More recently, through trio-based exome sequencing undertaken by the Deciphering Developmental Disorders Study (DDD study), a further 11 children with de novo CSNK2A1 variants have been identified. We have undertaken detailed phenotyping of these patients.

Variable developmental delays and characteristic facial features-A novel 7p22.3p22.2 microdeletion syndrome?

Isolated 7p22.3p22.2 deletions are rarely described with only two reports in the literature.

Structural analysis of pathogenic mutations in the DYRK1A gene in patients with developmental disorders.

Haploinsufficiency in DYRK1A is associated with a recognizable developmental syndrome, though the mechanism of action of pathogenic missense mutations is currently unclear. Here we present 19 de novo mutations in this gene, including five missense mutations, identified by the Deciphering Developmental Disorder study. Protein structural analysis reveals that the missense mutations are either close to the ATP or peptide binding-sites within the kinase domain, or are important for protein stability, suggesting they lead to a loss of the protein's function mechanism.

De Novo Loss-of-Function Mutations in USP9X Cause a Female-Specific Recognizable Syndrome with Developmental Delay and Congenital Malformations.

Mutations in more than a hundred genes have been reported to cause X-linked recessive intellectual disability (ID) mainly in males. In contrast, the number of identified X-linked genes in which de novo mutations specifically cause ID in females is limited. Here, we report 17 females with de novo loss-of-function mutations in USP9X, encoding a highly conserved deubiquitinating enzyme.

Further delineation of the KAT6B molecular and phenotypic spectrum.

KAT6B sequence variants have been identified previously in both patients with the Say-Barber-Biesecker type of blepharophimosis mental retardation syndromes (SBBS) and in the more severe genitopatellar syndrome (GPS). We report on the findings in a previously unreported group of 57 individuals with suggestive features of SBBS or GPS. Likely causative variants have been identified in 34/57 patients and were commonly located in the terminal exons of KAT6B.

EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations.

Background: Pontocerebellar hypoplasia (PCH) represents a group of neurodegenerative disorders with prenatal onset. Eight subtypes have been described thus far (PCH1-8) based on clinical and genetic features. Common characteristics include hypoplasia and atrophy of the cerebellum, variable pontine atrophy, and severe mental and motor impairments.

Subdural effusions and lack of early pontocerebellar hypoplasia in siblings with RARS2 mutations.

Mutations in the recently described RARS2 gene encoding for mitochondrial arginyl-transfer RNA synthetase give rise to a disorder characterised by early onset seizures, progressive microcephaly and developmental delay. The disorder was named pontocerebellar hypoplasia type 6 (PCH6) based on the corresponding radiological findings observed in the original cases. We report two siblings with the RARS2 mutation who displayed typical clinical features of PCH6, but who had distinct neuroimaging features.

Milder phenotypes of glucose transporter type 1 deficiency syndrome.

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a treatable condition resulting from impaired glucose transport into the brain. The classical presentation is with infantile-onset epilepsy and severe developmental delay. Non-classical phenotypes with movement disorders and early-onset absence epilepsy are increasingly recognized and the clinical spectrum is expanding.

Pain relief for the removal of femoral sheath in interventional cardiology adult patients.

Background: There is considerable variation in use of pain relief for managing pain or discomfort of femoral sheath removal. Efficacy of pain relief to promote comfort during this procedure or to reduce the incidence of vascular and procedural complications has not been established.

Objectives: Assess efficacy of pain relief used to manage pain of femoral sheath removal in adults after interventional cardiology.

Clinical and radiological findings in Schinzel-Giedion syndrome.

The absence of a definitive genetic test for the autosomal recessive condition Schinzel-Giedion syndrome is a significant handicap to the recognition of this disorder. Radiological features have been an important aspect of many of the published cases. In a series of six cases, we now establish a consistency among many of the radiological features in affected cases which will be an important diagnostic aid in identifying future cases.

Characterization of a recurrent 15q24 microdeletion syndrome.

We describe multiple individuals with mental retardation and overlapping de novo submicroscopic deletions of 15q24 (1.7-3.9 Mb in size).

Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome.

Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic disorders. We tested 290 individuals with mental retardation by BAC array comparative genomic hybridization and identified 16 pathogenic rearrangements, including de novo microdeletions of 17q21.

Vessel caliber and restenosis: a prospective clinical and angiographic study of NIR stent deployment in small and large coronary arteries in the same patient.

Retrospective analyses of patient cohorts undergoing stent deployment have shown that small vessel diameter and long lesion length are two angiographic predictors of increased restenosis. We determined the effects of these factors in patients with lesions treated in both small- and large-diameter coronary arteries. This multicenter prospective quantitative angiographic study evaluated patients with de novo coronary disease undergoing intervention who had at least two lesions < or = 16 mm length, one in a vessel < or = 2.

Employing children's nurses?

In 1994, the UKCC directed employers 'only to appoint persons into posts for which they have been appropriately by their programme of education and training leading to registration'. As part of a larger study into the expectations that NHS organisations have of newly qualified children's nurses, data were collected on the nursing registrations employers stipulated when wishing to appoint D grade staff to their children's wards. The survey was initially undertaken in 1998 and repeated in 2002.

Chromosome 7p disruptions in Silver Russell syndrome: delineating an imprinted candidate gene region.

Silver-Russell syndrome (SRS) is characterised by pre- and postnatal growth restriction (PNGR) and additional dysmorphic features including body asymmetry and fifth finger clinodactyly. The syndrome is genetically heterogeneous, with a number of chromosomes implicated. However, maternal uniparental disomy for chromosome 7 has been demonstrated in up to 10% of all cases.

Six-month angiographic and 12-month clinical follow-up of MultiLink long (25 to 35 mm) stents for long coronary narrowings in patients with angina pectoris.

There are limited prospective angiographic data on stent deployment for long coronary lesions. This multicenter prospective study enrolled 120 patients with a single de novo stenosis >20 mm in length, in a native vessel > or =3 mm diameter, suitable for a MultiLink stent 25 to 35 mm in length with additional stent deployment if required. Quantitative angiography before and immediately after stenting and at 6-month follow-up assessed restenosis for the complete lesion and for 5-mm segments of the stented and adjacent nonstented vessel.