Carrier screening has historically assessed a relatively small number of autosomal recessive and X-linked conditions selected based on frequency in a specific subpopulation and association with severe morbidity or mortality. Advances in genomic technologies enable simultaneous screening of individuals for several conditions. The American College of Medical Genetics and Genomics recently published a clinical practice resource that presents a framework when offering screening for autosomal recessive and X-linked conditions during pregnancy and preconception and recommends a tier-based approach when considering the number of conditions to screen for and their frequency within the US population in general.
View Article and Find Full Text PDFassociated familial platelet disorder (FPD) is a rare autosomal dominant hematologic disorder characterized by thrombocytopenia and/or altered platelet function. There is an increased propensity to develop myeloid malignancy (MM) - acute myeloid leukemia, myeloproliferative neoplasms or myelodysplastic syndrome often in association with secondary somatic variants in other genes. To date, 23 FPD-MM pediatric cases have been reported worldwide.
View Article and Find Full Text PDFBackground: Proliferation of large granular lymphocytes (LGL) and T-cell LGL (T-LGL) in peripheral blood along with demonstration of clonality are the hallmarks of a heterogeneous group of disorders, including T-LGL leukemia or T-LGL lymphocytosis. They are often associated with neutropenia and responsive to immunosuppression. The true nature of this entity is not well understood.
View Article and Find Full Text PDFBackground: The current risk stratification systems used to guide management of endometrial cancer are based on irreproducible post surgical pathological information, hence the need for more reliable classification systems. Using microarray and sequencing technologies, TCGA recently identified four prognostically significant endometrial carcinoma subtypes, which subsequently proved reproducible using clinically applicable surrogate tests. Using these tests, we sought to determine the level of concordance between endometrial biopsies and subsequent hysterectomy specimens in assessing the molecular classification of endometrial carcinoma.
View Article and Find Full Text PDFAcquired pure red cell aplasia and acquired amegakaryocytic thrombocytopenic purpura are rare in children. Similarly, clonal expansion of T-cell large granular lymphocytes is infrequently seen in pediatrics. Lipopolysaccharide-responsive beige-like anchor (LRBA) protein deficiency is a recently described immunodeficiency syndrome that has been associated with inflammatory bowel disease and autoimmune phenomena such as Evans syndrome.
View Article and Find Full Text PDFJ Natl Compr Canc Netw
October 2017
With the rapid development of precision medicine, next-generation sequencing (NGS) has provided the ability to uncode tumors at the DNA level. Identifying mutations and other molecular changes has become more crucial in the management of non-small cell lung cancer (NSCLC) than ever before. Although the histologic subtypes in patients with advanced NSCLC remain valid in determining treatment options, the detection of specific molecular signatures such as de novo T790M with sensitizing mutations could be more useful than the histologic subtype itself.
View Article and Find Full Text PDFTriple-primed PCR assays have become the preferred fragile X syndrome testing method. Using a commercially available assay, we detected a reproducible extra peak(s) in 0.5% of 13,161 clinical samples.
View Article and Find Full Text PDFOn the basis of previous studies suggesting that vascular endothelial growth factor (VEGF) could protect motor neurons from degeneration, adeno-associated virus vectors (serotypes 1 and 9) encoding VEGF (AAV.vegf) were administered in a limb-expression 1 (LIX1)-deficient cat-a large animal model of lower motor neuron disease-using three different delivery routes to the central nervous system. AAV.
View Article and Find Full Text PDFFeline spinal muscular atrophy (SMA) is a fully penetrant, autosomal recessive lower motor neuron disease in domestic cats that clinically resembles human SMA Type III. A whole genome linkage scan identified a ∼140-kb deletion that abrogates expression of LIX1, a novel SMA candidate gene of unknown function. To characterize the progression of feline SMA, we assessed pathological changes in muscle and spinal cord from 3 days of age to beyond onset of clinical signs.
View Article and Find Full Text PDFFeline spinal muscular atrophy (SMA) is an autosomal recessive juvenile onset lower motor neuron disease caused by an ∼ 140 kb deletion that disrupts expression of 2 genes, limb expression 1 (LIX1) and leucyl/cystinyl aminopeptidase (LNPEP). A previously generated Lnpep knockout (KO) mouse did not demonstrate a neuromuscular phenotype. Little is known about LIX1, except that it is evolutionarily conserved and highly expressed in spinal cord motor neurons.
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