MedGen

Functional anomaly of the kidney persisting for at least three months. [from HPO]

The atherogenic lipoprotein phenotype (ALP) is a common heritable trait characterized by a preponderance of small, dense low density lipoprotein (LDL) particles (subclass pattern B), increased levels of triglyceride-rich lipoproteins, reduction in high density lipoprotein, and a 3-fold increased risk of myocardial infarction (summary by Nishina et al., 1992). The so-called atherogenic lipoprotein phenotype was shown by Austin et al. (1988) to be independently associated with an increased risk for coronary artery disease. Allayee et al. (1998) concluded, furthermore, that there is a genetically based association between familial combined hyperlipidemia (FCHL; 144250) and small, dense LDL particles and that the genetic determinants for LDL particle size are shared, at least in part, among FCHL families and the more general population at risk for coronary artery disease. Juo et al. (1998) concluded from a bivariate segregation analysis of small, dense LDL particles and elevated apolipoprotein B levels (APOB; 107730), which are commonly found together in members of FCHL families, that the 2 traits share a common major gene plus individual polygenic components. The common major gene was estimated to explain 37% of the variance of adjusted LDL particle size and 23% of the variance of adjusted apoB levels. [from OMIM]

Autoimmune lymphoproliferative syndrome (ALPS), caused by defective lymphocyte homeostasis, is characterized by the following: Non-malignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly with or without hypersplenism) that often improves with age. Autoimmune disease, mostly directed toward blood cells. Lifelong increased risk for both Hodgkin and non-Hodgkin lymphoma. In ALPS-FAS (the most common and best-characterized type of ALPS, associated with heterozygous germline pathogenic variants in FAS), non-malignant lymphoproliferation typically manifests in the first years of life, inexplicably waxes and wanes, and then often decreases without treatment in the second decade of life; in many affected individuals, however, neither splenomegaly nor the overall expansion of lymphocyte subsets in peripheral blood decreases. Although autoimmunity is often not present at the time of diagnosis or at the time of the most extensive lymphoproliferation, autoantibodies can be detected before autoimmune disease manifests clinically. In ALPS-FAS caused by homozygous or compound heterozygous (biallelic) pathogenic variants in FAS, severe lymphoproliferation occurs before, at, or shortly after birth, and usually results in death at an early age. ALPS-sFAS, resulting from somatic FAS pathogenic variants in selected cell populations, notably the alpha/beta double-negative T cells (a/ß-DNT cells), appears to be similar to ALPS-FAS resulting from heterozygous germline pathogenic variants in FAS, although lower incidence of splenectomy and lower lymphocyte counts have been reported in ALPS-sFAS and no cases of lymphoma have yet been published. [from GeneReviews]