Heterozygous DLX5 nonsense mutation associated with isolated split-hand/foot malformation with reduced penetrance and variable expressivity in two unrelated families.

BACKGROUND: Split-hand/foot malformation (SHFM) is a clinically and genetically heterogeneous limb abnormality characterized by the absence or hypoplasia of the central rays of the autopod. SHFM1, which is one out of seven known SHFM loci, maps to 7q21.2-q21.3. SHFM1 is usually inherited as an autosomal dominant trait with reduced penetrance, although recessive inheritance has been described for a single family carrying a homozygous DLX5 missense variant. In most cases, SHFM1 results from heterozygous deletions encompassing DLX5/DLX6 genes or from inversions and translocations separating the genes from their limb specific enhancers. Recently, a single Chinese family with dominant SHFM1 was shown to result from a heterozygous DLX5 missense mutation. METHODS: In this study, we report on four male individuals from two unrelated Polish families (one sporadic and one familial case) presenting with isolated SHFM. We tested both probands for known molecular causes of SHFM, including TP63, WNT10B, DLX5 mutations and copy number changes using 1.4 M array CGH. RESULTS: Sanger sequencing of DLX5 revealed a novel heterozygous nonsense mutation c.G115T(p.E39X) in both index patients. Segregation studies demonstrated that the variant was present in all affected family members but also in three apparently healthy relatives (two females and one male). CONCLUSION: This is the first report of a heterozygous DLX5 nonsense mutation resulting in incompletely penetrant autosomal dominant isolated SHFM1. Data shown here provides further evidence for the contribution of DLX5 point mutations to the development of ectrodactyly and suggest the possibility of sex-related segregation distortion with an excess of affected males.

Introducing of the First DCD Kidney Transplantation Program in Poland.

In many countries, including Poland, the main problem with transplantation is the insufficiency of organ donors in relation to the demand for organs. Hence, the common aim globally is to increase the pool of donors. The prolonged survival of patients after transplantation, with respect to the survival time of patients on dialysis, makes the search much more intense. After the recourse of expanded criteria donors (ECD), the next step was obtaining kidneys from donors after irreversible cardiac death (DCD). Therefore, based on Dutch, British, and Spanish experience, it can be hypothesized that the introduction of DCD procedures in countries that have not launched these programs and the improvement of DCD procedures may shorten the waiting time for organ transplantation globally. The legal basis for the procurement of organs after irreversible cardiac arrest came into existence in Poland in 2010. Previously, such organ procurements were not in practice. Since 1984, when Poland published irreversible cardiac arrest as a criterion of brain death, it became the only way to determine death prior to the procurement of organs. The aim of this report was to evaluate the results of the first 19 transplantation cases involving harvested kidneys from donors after cardiac arrest, which was irreversible and clinically confirmed, without any doubt as per the ethical protocol of DCD. Understanding, support, and public perception are essential for this program's initiation and maintenance.

Endovascular Abdominal Aortic Aneurysm Repair in a Kidney Transplant Patient After an Iatrogenic Iliac Artery Dissection.

A 64-year-old man who had undergone a renal transplant 9 years earlier, was admitted to our hospital because of an asymptomatic, large, abdominal aortic aneurysm. During an introduction of a guide wire to the left common femoral artery dissection of iliac artery occurred with occlusion of graft renal artery. And endarterectomy of the common, external, and internal iliac arteries was performed, with no sufficient kidney inflow. A bypass was performed between the common iliac and the left common femoral artery with a kidney artery reanastomosis to the prosthesis. After 4 months of endovascular treatment of the aortic aneurysm, the patient's renal function remained unchanged.