Project description:Autosomal recessive polycystic kidney disease (ARPKD) is a severe renal cystic disease mainly caused by PKHD1. However, its genetic cause, pathological features, and mechanism remained unsolved. Our findings may provide new insight on the pathophysiology of the polycystic kidney due to PKHD1 deficiency, and the PKHD1 mosaicism needs to be taken close attention in genetic testing of ARPKD.
Project description:NGlY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder, and liver dysfunction. To better understand disease pathogensis and neurological symptoms of NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with disease causing mutations.
Project description:Pompe disease (glycogen storage disease type II, or acid maltase deficiency) is an autosomal-recessive disorder of metabolism caused by mutations in the lysosomal hydrolase, acid alpha-glucosidase gene (GAA), resulting in progressive muscle atrophy. Gene therapy is a promising approach to treat genetic diseases, and liver-restricted expression of secretable GAA can produce immune tolerance and improve muscle GAA activity. To further understand the molecular mechanisms underlying Pompe disease and impact of gene therapy, we applied RNA sequencing.
Project description:Familial thyroid cancer originating from follicular cells accounts for 5-15% of all the thyroid carcinoma cases in humans. Previously, we described thyroid follicular cell carcinomas in a large number of the Dutch German longhaired pointers (GLPs) with likely an autosomal recessive inheritance pattern. Here, we investigated the genetic causes of the disease using a combined approach of genome-wide association study, selective sweep analysis, and ROH analysis based on 170k SNP array genotype data. A region 0-5 Mb on chromosome 17 harboring the TPO gene was identified to be associated with the disease.
Project description:We identified 18 patients with the distinct clinical phenotype of disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis and molds. This syndrome typically had its onset in adulthood and was characterized by profound circulating monocytopenia, B lymphocytopenia, and NK lymphocytopenia. T lymphocytes were variably affected. Despite these peripheral cytopenias, all patients had macrophages and plasma cells at sites of inflammation and normal immunoglobulin levels. This novel clinical syndrome links mycobacterial, viral, and fungal susceptibility with malignancy and is transmitted in an autosomal dominant pattern. In order to elucidate the possible genetic defect that results in this novel clinical syndrome, we performed microarray expression analysis on polymorphonuclear leukocytes (PMNs) isolated from affected patients and healthy controls. Keywords: healthy donor vs affected patient
Project description:Spinal Muscular Atrophy (SMA) is an autosomal recessive motor neuron disease and is the second most common genetic disorder leading to death in childhood. No effective therapy is currently available. It has been suggested that β-lactam antibiotics such as ceftriaxone may offer neuroprotection in motoneuron disease. We investigated the therapeutic effect of ceftriaxone in a murine model of SMA. Microarray technology was used to assess the global gene expression profile of spinal cord obtained by ceftriaxone-treated and vehicle treated SMA mice.