A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia.

Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL), but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.

Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis.

Gaucher disease (GD), an inherited macrophage glycosphingolipidosis, manifests with an extraordinary variety of phenotypes that show imperfect correlation with mutations in the GBA gene. In addition to the classic manifestations, patients suffer from increased susceptibility to hematologic and nonhematologic malignancies. The mechanism(s) underlying malignancy in GD is not known, but is postulated to be secondary to macrophage dysfunction and immune dysregulation arising from lysosomal accumulation of glucocerebroside.

Pulmonary vascular disease in Gaucher disease: clinical spectrum, determinants of phenotype and long-term outcomes of therapy.

Pulmonary arterial hypertension (PAH) and hepatopulmonary syndrome (HPS) are rare pulmonary vascular complications of type 1 Gaucher disease (GD1). We examined GBA1 genotype, spleen status, Severity Score Index (SSI), and other patient characteristics as determinants of GD/PAH-HPS phenotype. We also examined the long-term outcomes of imiglucerase enzyme replacement therapy (ERT) +/- adjuvant therapies in 14 consecutive patients.

Misdiagnosis of Niemann-Pick disease type C as Gaucher disease.

Niemann-Pick disease type C (NPC) is a model for inborn errors of metabolism whose gene product mediates molecular trafficking rather than catabolizing macromolecules, as in classic lipidoses. We report the case of an infant who presented with hepatosplenomegaly without neurological abnormalities. Decreased activity of acid β-glucosidase and elevated serum chitotriosidase and tartrate-resistant acid phosphatase on repeated measurements led to initial diagnosis of Gaucher disease (GD).

Expanding spectrum of the association between Type 1 Gaucher disease and cancers: a series of patients with up to 3 sequential cancers of multiple types--correlation with genotype and phenotype.

In Gaucher disease (GD), inherited deficiency of lysosomal glucocerebrosidase due to mutations in GBA1 gene results in accumulation of glucosylceramide in tissue macrophages, systemic macrophage activation, and a complex multisystemic phenotype. We and others have reported an increased risk of multiple myeloma and other malignancies in non-neuronopathic Type 1 GD (GD1). Here, we describe a subset of GD1 patients with multiple malignancies.