Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present two siblings with identical clinical findings that seem to represent a previously unreported familial syndrome. Major findings involve three systems: pulmonary arterial hypertension, cardiac abnormalities including secundum-type atrial septal defect, and the hematopoietic system with intermittent neutropenia, lymphopenia, monocytosis, and anemia. The siblings also shared several minor abnormalities: pectus carinatum, long fingers, proximally placed thumb, broad nasal bridge, and high-arched palate. The male proband also had bilateral inguinal hernias and undescended testes. The same findings in two siblings suggest a genetic cause--either an autosomal recessive disorder or germline mosaicism in one parent for a dominant mutation. Investigations revealed a bone morphogenetic protein receptor 2 polymorphism in intron 4 in only one sibling, which was also present in unaffected maternal relatives.
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PMID:Familial pulmonary arterial hypertension, leucopenia, and atrial septal defect: a probable new familial syndrome with multisystem involvement. 1901 69

SIRT6 has been identified as an H3K9 deacetylase and a critical regulator of genome stability, telomere integrity, and metabolic homeostasis. Sirt6-deficient mice displayed dramatic phenotypes including profound lymphopenia, loss of subcutaneous fat, lordokyphosis and low bone marrow density. Here, we report that SIRT6 regulates osteogenic differentiation independent of its deacetylase activity in vitro. Further mechanistic studies showed that SIRT6 involves the cell fate determination by modulating bone morphogenetic protein (BMP) signaling. Unexpectedly, this modulation depends upon P300/CBP-associated factor (PCAF). In addition, we observed impaired SIRT6 expression in bone marrow mesenchymal stem cells and in bone sections of ovariectomized mice. Taken together, our present study provide new insights into mechanisms of SIRT6-regulated MSC function beyond its H3K9 deacetylase activity.
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PMID:SIRT6 promotes osteogenic differentiation of mesenchymal stem cells through BMP signaling. 2886 May 94