Genetics, pathogenesis and complications of XXXX .

@entity1 @entity154 @entity227 @entity851 @entity50849 @entity7464 @entity5298 @entity2850 @entity177 @entity79 @entity600 @entity179 @entity74 @entity2527 @entity61350 @entity25015 @entity16455 @entity34185 @entity2525
@entity1 @entity2525 is a rare @entity74 caused by @entity177 , which ranges widely in severity. In the most severe forms, @entity2527 prevents @entity79 , impairing development of bone marrow, leading to hematological failure. Closure of bone foramina causes @entity2850 with @entity227 . @entity1 also present with @entity16455 , @entity851 , @entity600 and brittle bones. This form is fatal in infancy, has an autosomal recessive inheritance and is cured with hematopoietic stem cell transplantation, with a rate of success <50% and unsatisfactory rescue of growth and @entity227 . It relies on loss-of-function mutations of various genes, including the @entity25015 gene, encoding for the a3 subunit of the H+ATPase and accounting for >50% of cases, the @entity50849 and the @entity61350 genes, which have closely related function and account for approximately 10% of cases, also presenting with @entity179 . Further genes are implicated in rare forms with various severities and association with other syndromes and, recently, the @entity5298 gene has been found to be mutated in a subset of @entity1 lacking osteoclasts. @entity74 may also have intermediate severity, with a small number of cases due to loss-of-function mutations of the @entity7464 or the @entity34185 genes. Dominant negative mutations of the @entity50849 gene cause the so-called Albers-Sch  nberg disease, which represents the most frequent and heterogeneous form of @entity2525 , ranging from asymptomatic to intermediate/severe, thus suggesting additional genetic/environmental determinants affecting penetrance. Importantly, recent work has demonstrated that osteoblasts may also contribute to the pathogenesis of the disease, either because they are affected by @entity154 , or because their activity may be enhanced by deregulated osteoclasts abundantly present in most forms. Therapy is presently unsatisfactory and effort is necessary to unravel the gene defects yet unrecognized and identify new treatments to improve symptoms and save life.
