Pedigrees of families where underlying genetic mutations were not identified.

<p>(a) Family pedigree of patient 22538 diagnosed with CORD. (b) Family pedigree of patient 26309 diagnosed with RP. (c) Family pedigree of patient 23609 diagnosed with CORD.</p

Analysis of alternative splicing <i>in vitro</i>.

<p><b>(a)</b> Primer design to capture putative intron retention due to c.439-17G>A variant in <i>CDHR1</i>. <b>(b)</b> Agarose gel electrophoresis of RT-PCR showing a 140bp PCR product only in the patient cell-line (white asterix). No products were seen in control cell line or water control. <b>(c)</b> Bottom: Sequence chromatograph shows a clear retention of 15bp from intron 5 in the RT-PCR product, generated due to the cryptic splice-site activation. Top: Schematic representing the exon-intron boundaries as observed in the RT-PCR product.</p

Prediction scores of canonical (c.439) and cryptic splice site (c.439-17) by five prediction algorithms due to the variant c.439-17G>A in <i>CDHR1</i> gene.

<p>Prediction scores of canonical (c.439) and cryptic splice site (c.439-17) by five prediction algorithms due to the variant c.439-17G>A in <i>CDHR1</i> gene.</p

Clinical phenotypes of patient, variant descriptions and pathogenicity prediction of the variants identified in this study.

<p>Clinical phenotypes of patient, variant descriptions and pathogenicity prediction of the variants identified in this study.</p

<i>CDHR1</i> intronic variant.

<p>Snapshot of Alamut visual showing an intronic variant (c.439-17G>A) in patient 26007 (green rectangle). The bam alignment file clearly shows a heterozygous variant 17bp upstream from exon 6. Inset: Snapshot of splicing prediction algorithms (<i>in silico</i>) shows a strong cryptic splice acceptor gain at the site of the variant (blue rectangle). Values are comparable to that of canonical splice acceptor site. Red rectangle shows a stop codon in-frame to the cryptic splice activator site.</p

Patient pedigrees and sequence chromatography of identified disease-associated variants.

<p>Variants are denoted as M6, M7 and M8. <b>(a)</b> Family pedigree of patient 26007. <b>(b)</b> Sequence chromatography of heterozygous <i>CDHR1</i> variant c.398C>G in patient (bottom), carrier mother (middle) and father (top). <b>(c)</b> Sequence chromatography of heterozygous <i>CDHR1</i> variant c.439-17G>A in patient (bottom), mother (middle) and carrier father (top). <b>(d)</b> Predicted structure of CDHR1 reference protein (in blue) aligned to mutant CDHR1 (p.Pro133Arg) (in orange). The mutation is shown by magenta spheres and is localized within the first cadherin domain (white rectangle). <b>(e)</b> A zoomed image of the first cadherin domain of CDHR1 shows an additional beta-sheet (white arrow) close to the mutation <b>(f)</b> Family pedigree of patient 23530. <b>(g)</b> Agarose gel image of <i>PRPF31</i> exon 7 PCR shows a larger band only in affected members indicating a duplication. C = Water control in PCR. <b>(h)</b> Comparison of predicted models of the PRPF31 reference protein sequence (i & v, in green), mutant PRPF31 (ii & vi, in magenta), alignment of reference and mutant PRPF31(iii & viii) and zoomed image of the alignment at the mutation site (iv & viii). An additional turn of the mutant in the coiled-coil domain is depicted in white. The first amino acid of the 11bp duplication is shown by a white arrow. “N” denotes the N-terminus of the protein.</p

Sex-specific inequalities in the treatment of severely calcified coronary lesions: a sub-analysis of the PREPARE-CALC trial

Background: Coronary vessels in women may have anatomical and histological particularities. The aim of this study was to investigate sex-specific characteristics and outcomes of patients with calcified coronary arteries in the Prepare-CALC (Comparison of Strategies to Prepare Severely Calcified Coronary Lesions) trial.  Methods: The Prepare-CALC trial randomised patients with severe coronary calcification to coronary lesion preparation either using modified balloons (MB; cutting or scoring) or rotational atherectomy (RA).  Results: Of 200 randomised patients, 24% were women. Strategy success in general was similar between women (93.8%) and men (88.2%; p=0.27). For men, strategy success was significantly more common with an RA-based strategy than an MB-based strategy (98.7% in the RA group versus 77.3% in the MB group, p0.99, p for interaction between sex and treatment strategy=0.03). Overall, significant complications such as death, MI, stent thrombosis, bypass operation and perforations were rare and did not differ significantly by gender or treatment strategy. Plaque rupture and disrupted calcified nodules were more common in women.  Conclusion: In a well-defined patient population with severely calcified coronary arteries, lesion preparation with an RA-strategy was superior to an MB-strategy in men. For women, both RA and MB strategies appear to have a similar success rate, although definitive conclusions are limited due to the small number of women in the trial. </p

Additional file 1 of Cardiovascular magnetic resonance-derived left atrioventricular coupling index and major adverse cardiac events in patients following acute myocardial infarction

Additional file 1: Figure S1. Kaplan–Meier curves for survival analyses in subgroup of low-risk patients. Left atrioventricular coupling index (LACI) and survival in low-risk patients according to left ventricular ejection fraction (LVEF) after acute myocardial infarction. Incidence of MACE (major adverse cardiac events) according to high and low LACI classified according to Youden Index

Pedigree and mutation segregation.

<p>All patients exhibiting symptoms of HHR are homozygous for the mutation <i>SLC34A3</i> p.G196R (c.586G>A NM_080877.2), whereas all patients expressing symptoms of CM are homozygous for the mutation <i>SEPN1</i> p.G239R (c.715G>A NM_206926.1). Therefore, patients II-2 and II-7 present features of both diseases. Arrows indicate index patients. Abbreviations: HHR = Hereditary hypophosphatemic rickets; CM = congenital myopathy.</p

<i>RBFOX1and RBFOX3</i> variants and phenotype of index-patients.

<p>Survey on <i>RBFOX1</i> and <i>RBFOX3</i> variants in patients. Seizure type and comorbidity overview of variant carrier. Abbreviations: RE = rolandic epilepsy; CTS = centrotemporal spikes; ESES = epileptic encephalopathy with status epilepticus during sleep.</p