Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Floating-Harbor syndrome (FHS) is a rare genetic disorder recently shown to be caused by mutations in the Snf2-related CREB-binding protein activator protein gene (SRCAP). It comprises three key clinical features of characteristic facies, expressive and receptive speech impairment and short stature. We report on a patient with this syndrome associated with early adult-onset hypertension and bilateral polycystic kidneys. Family screening for polycystic kidney disease was negative and mutations in polycystic kidney disease 1 and 2 genes (PKD1 and PKD2) were absent. Sequencing of the SRCAP gene demonstrated a de novo mutation matching one of the known FHS-associated mutations. The patient required treatment with anti-hypertensives and will require lifelong renal monitoring. We suggest this patient's presentation may be due to the pleiotropic effects of SRCAP mutations. Further, the protein encoded by SRCAP is known to interact with CREB-binding protein, the product of the gene mutated in Rubinstein-Taybi syndrome, which is associated with renal abnormalities. A literature review of the renal findings in patients with Floating-Harbor syndrome identified another patient with possible polycystic kidneys, two patients with early onset hypertension, and a young patient with a ruptured intracranial aneurysm, which can be a feature of classic adult polycystic kidney disease. Collectively, these findings suggest that all patients with Floating-Harbor syndrome should undergo regular blood pressure monitoring and screening for polycystic kidneys by ultrasound at the time of the FHS diagnosis with imaging to be repeated during adulthood if a childhood ultrasound was negative.
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PMID:Floating-Harbor syndrome and polycystic kidneys associated with SRCAP mutation. 2316 45

Floating-Harbor syndrome (FHS) is a rare autosomal dominant disorder characterized by short stature, skeletal malformations, speech delay, and dysmorphic facial appearance. Recently, mutations in SRCAP encoding a coactivator for cAMP-response element binding protein (CREB)-binding protein have been identified in small number of patients with FHS. Here, we report on long-term follow-up data of a male patient with a SRCAP mutation. The patient presented with mild hypothyroidism and renal hypouricemia, in addition to several FHS-compatible features including growth impairment, cognitive disability, facial dysmorphisms, and hypertension. He showed delayed bone age from infancy to 9 years of age and markedly accelerated bone age with the formation of cone-shaped epiphyses and early epiphysial fusions after the onset of puberty. His pubertal sexual development was almost age appropriate. Two-year treatment with growth hormone (GH) did not significantly improve the growth velocity. Molecular analysis identified a de novo heterozygous nonsense mutation (p.R2444X) in the last exon of SRCAP, which has been most common mutation detected in patients from other ethnic groups. These results indicate that perturbed skeletal maturation from infancy through adolescence is a characteristic feature in patients with SRCAP mutations. Furthermore, our data imply that GH therapy exerted only a marginal effect on the growth of this patient, and that renal hypouricemia may be a novel complication of FHS.
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PMID:Long-term follow-up study for a patient with Floating-Harbor syndrome due to a hotspot SRCAP mutation. 2437 13

Floating-Harbor syndrome (FHS) is a rare, heritable disorder caused by variants in the SRCAP gene. Most individuals with FHS have characteristic facial features, short stature, and speech and language impairment. Although FHS has been likely under-diagnosed due to a combination of lack of recognition of the clinical phenotype and limited access to genomic testing, it is a rare condition with around 100 individuals reported in the medical literature. Case series have been biased towards younger individuals (vast majority <20 years of age) meaning that it has been challenging to provide accurate medical advice for affected individuals in adulthood. We report two young adults with FHS who presented with intracranial haemorrhage likely secondary to cerebrovascular aneurysms, with devastating consequences, making a total of four FHS patients reported with significant cerebrovascular abnormalities. Three of four patients had hypertension, at least one in conjunction with normal renal structure. We consider possible relationships between hypertension, renal pathology and aneurysms in the context of FHS, and consider mechanisms through which disruption of the SRCAP protein may lead to vascular pathology. We recommend that clinicians should have a low threshold to investigate symptoms suggestive of cerebrovascular disease in FHS. We advise that patients with FHS should have annual blood pressure monitoring from adolescence, renal ultrasound at diagnosis repeated in adulthood, and timely investigation of any neurological symptoms. For patients with FHS, particularly with hypertension, we advise that clinicians should consider at least one MRA (Magnetic Resonance Imaging with Angiography) to check for cerebral aneurysms.
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PMID:Intracranial vascular pathology in two further patients with Floating-Harbor syndrome: Proposals for cerebrovascular disease risk management. 3160 16