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Biallelic loss-of-function variants in the SMG9 gene, encoding a regulatory subunit of the mRNA nonsense-mediated decay (NMD) machinery, are reported to cause heart and brain malformation syndrome. Here we report five patients from three unrelated families with intellectual disability (ID) and a novel pathogenic SMG9 c.551 T > C p.(Val184Ala) homozygous missense variant, identified using exome sequencing. Sanger sequencing confirmed recessive segregation in each family. SMG9 c.551T > C p.(Val184Ala) is most likely an autozygous variant identical by descent. Characteristic clinical findings in patients were mild to moderate ID, intention tremor, pyramidal signs, dyspraxia, and ocular manifestations. We used RNA sequencing of patients and age- and sex-matched healthy controls to assess the effect of the variant. RNA sequencing revealed that the SMG9 c.551T > C variant did not affect the splicing or expression level of SMG9 gene products, and allele-specific expression analysis did not provide evidence that the nonsense mRNA-induced NMD was affected. Differential gene expression analysis identified prevalent upregulation of genes in patients, including the genes SMOX, OSBP2, GPX3, and ZNF155. These findings suggest that normal SMG9 function may be involved in transcriptional regulation without affecting nonsense mRNA-induced NMD. In conclusion, we demonstrate that the SMG9 c.551T > C missense variant causes a neurodevelopmental disorder and impacts gene expression. NMD components have roles beyond aberrant mRNA degradation that are crucial for neurocognitive development.

Zusammenfassung: Nach einem anfänglich gemeinsamen Weg in der Fistelchirurgie begann in den USA ab etwa 1975 der bevorzugte Einsatz von Prothesenshunts. In bis zu 80% wurden bei Erstoperationen Gefäßprothesen implantiert, mit entsprechend hoher Komplikationsrate und hohen Folgekosten. Europa pflegte, mit lokalen Unterschieden, das Konzept der vorzugsweisen Verwendung von arteriovenösen Fisteln weiter (AVF). Der Prothesenanteil war nie höher als 40%. Unterstützt von Richtlinien, versuchen die USA seit 1997 einen deutlichen Umschwung herbeizuführen. Der Anteil primärer AVF ist seither angestiegen, bei allerdings wohl erhöhter initialer Versagerquote im internationalen Vergleich. Über Richtlinien hinaus sollte für beide Kontinente als vordringliche Aufgaben die interdisziplinäre Zusammenarbeit aller beteiligten Fachgebiete gelten: Durchführung zertifizierter, interdisziplinärer Kurse mit konsensfähigen Inhalten, Einrichtung von Referenzzentren mit einheitlicher, umfassender Dokumentation, Aufbau von Datenbanken zur Qualitätskontrolle mit abrufbaren Komplikations- und Funktionsraten, Standardisierung der Überwachung von Gefäßzugängen im Dialysezentrum

Background: Surgical profundaplasty (SP)is used mainly as an adjunct to endovascular management of peripheral vascular disease (PAD) today. Results from earlier series of profundaplasty alone have been controversial, especially regarding its hemodynamic effect. The question is: Can profundaplasty alone still be useful? Our aim was to evaluate its role in the modern management of vascular patients. Methods: This was a retrospective outcome study. A consecutive series of 97 patients (106 legs) from January 2000 through December 2003 were included. In 55 (52%) legs, the superficial femoral artery was occluded. These patients were included in the current analysis. Of these patients 14 (25%) were female. Mean age was 71 ((11) years. Nineteen (35%) were diabetic. The indication for operation was claudication in 29 (53%), critical leg ischemia (CLI) in 26 (47%), either with rest pain in 17 (31%), or ulcer/gangrene in 9 (16%). Endarterectomy with patch angioplasty with bovine pericardium was performed in all cases. Mean follow-up was 33(14 months. Mean preoperative ankle brachial index (ABI) was 0.6. Sustained clinical efficacy was defined as upward shift of 1 or greater on the Rutherford scale without repeat target limb revascularization (TLR) or amputation. Mortality, morbidity, need for TLR, or amputation were separate endpoints. Results: Postoperatively, ABI was significantly improved (mean=0.7), in 24 (44%) by more than 0.15. At three years, cumulative clinical success rate was 80%. Overall, patients with claudication had a better outcome than those with CLI (p=0.04). Two (4%) major amputations and 2 (4%) minor ones were performed, all in patients with CLI. None of the 9 (16%) ulcers healed. Conclusion: Profundaplasty is still a valuable option for patients with femoral PAD and claudication without tissue loss. It is a straightforward procedure that combines good efficacy with low complication rates. Further endovascular treatment may be facilitated. It is not useful f

Thirty serum samples from clinical cases of flour hypersensitivity were analyzed for wheat or rye flour protein antibodies. The patients included 20 bakers and 10 others who also had occupational flour exposure. Twenty-three cases had antiflour antibodies which recognized antigens other than control sera in the flour protein patterns. The immunologic response of individual cases seemed very variable in view of the numerous differences between the cases in the antigen-antibody reactions. For the practical purposes, the flour protein antigens were divided in three groups, i.e., those larger than 80 kDa, those between 80 and 50 kDa and those smaller than 50 kDa. Cases with flour-induced dermatitis (n=8) showed sensitization towards antigens in all size classes while those with rhinitis or asthma showed more antigens with a molecular weight less than 50 kDa. The test offers a possibility to independently verify an exposure to flour while it does not substitute for the conventional immunologic diagnostic tests