Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uniparental disomy (UPD) is the inheritance of a chromosome pair from one parent and is increasingly recognized as a cause of abnormal phenotypes either due to imprinted genes or, in the case of isodisomy, to homozygosity of recessive alleles. Maternal uniparental disomy for chromosome 14 (matUPD[14]) may cause a characteristic phenotype including precocious puberty. Central precocious puberty (CPP) was diagnosed in a 6-year-old girl with some dysmorphic features, truncal obesity, small hands, and small feet. Cytogenetic analysis of her peripheral blood demonstrated chromosomal rearrangement: Robertsonian translocation 45, XX, der(13;14)(q10;q10). MatUPD(14) was demonstrated in the patient by haplotype analysis of chromosome 14, showing that the CPP is one of the features caused by matUPD(14). The CPP was successfully treated with higher dosage of long-acting gonadotropin releasing hormone (GnRH) analogue, Leuprolide, 90 microg/kg/month. This is the first report that describes GnRH analogue treatment for CPP associated with matUPD(14), suggesting that the GnRH analogue treatment is appropriate even for such a specific type of CPP.
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PMID:Long-acting gonadotropin-releasing hormone analogue treatment for central precocious puberty in maternal uniparental disomy chromosome 14. 1627 4

Precocious puberty is defined as the appearance of secondary sex characteristics before 8 years of age in girls and before 9 years of age in boys. Central precocious puberty (CPP) is diagnosed when activation of the hypothalamic-pituitary axis is identified. It is a rare disease with a clear female predominance. A background of international adoption increases its risk, with other environmental factors such as endocrine disruptors also being associated with CPP. The causes of CPP are heterogeneous, with alterations of the CNS being of special interest. Physical injuries of the CNS are more frequent in boys, while idiopathic etiology is more prevalent among girls. However, in the last decade the number of idiopathic cases has diminished thanks to the discovery of mutations in different genes, including KISS1, KISS1R, MKRN3, and DLK1 that cause CPP. For the diagnosis of CPP, hormone studies are needed in addition to the clinical data regarding signs of pubertal onset. For this purpose, the GnRH test continues to be the gold standard. Imaging analyses, such as bone age and brain MRI, are also very useful. Furthermore, genetic testing must be incorporated in the diagnosis of CPP, especially in familial cases. Early puberty has been related to various consequences in the medium and long term such as behavioral problems, breast cancer, obesity, and metabolic comorbidities. However, there are few studies that have exclusively analyzed patients with CPP. GnRH analogs are the most frequent treatment election with the main objective being to improve adult height. Currently, there are new formulations that are being investigated.
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PMID:Central precocious puberty, functional and tumor-related. 3073 78

Pubertal timing in humans is determined by complex interactions including hormonal, metabolic, environmental, ethnic, and genetic factors. Central precocious puberty (CPP) is defined as the premature reactivation of the hypothalamic-pituitary-gonadal axis, starting before the ages of 8 and 9 years in girls and boys, respectively; familial CPP is defined by the occurrence of CPP in two or more family members. Pioneering studies have evidenced the participation of genetic factors in pubertal timing, mainly identifying genetic causes of CPP in sporadic and familial cases. In this context, rare activating mutations were identified in genes of the kisspeptin excitatory pathway (KISS1R and KISS1 mutations). More recently, loss-of-function mutations in two imprinted genes (MKRN3 and DLK1) have been identified as important causes of familial CPP, describing novel players in the modulation of the hypothalamic-pituitary-gonadal axis in physiological and pathological conditions. MKRN3 mutations are the most common cause of familial CPP, and patients with MKRN3 mutations present clinical features indistinguishable from idiopathic CPP. Meanwhile, adult patients with DLK1 mutations present high frequency of metabolic alterations (overweight/obesity, early onset type 2 diabetes and hyperlipidemia), indicating that DLK1 may be a novel link between reproduction and metabolism. Arch Endocrinol Metab. 2019;63(4):438-44.
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PMID:Pioneering studies on monogenic central precocious puberty. 3146 Jun 23