Cosegregation of a novel mutation in the sixth transmembrane segment of the luteinizing/choriogonadotropin hormone receptor with two Brazilian siblings with severe testotoxicosis

Siviero-Miachon, Adriana Aparecida; Kizys, Marina M. L.; Ribeiro, Mariana da Silva; García, F; Spinola-Castro, Ângela Maria; Silva, Magnus R. Dias da

doi:10.1080/07435800.2016.1217005

Cited by 11 publications

(8 citation statements)

References 29 publications

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“…It is a gonadotropin-independent precocious puberty characterized by rapid virilization, growth acceleration, bone age advance-ment, and elevated testosterone concentrations despite prepubertal concentrations of LH [7,19]. To date, 18 mutations in the LHCGR gene have been reported in boys with testotoxicosis, mostly located in exon 11, which differs from the results of our study [20]. The serum LH response to GnRH reflects the pubertal status: LH concentration 1 h post-GnRH agonist stimulation of ≥ 3.2 U/L is 90 % sensitive, and that of ≥ 5.5 U/L is 95 % specific for the onset of puberty in girls [21][22][23].…”

Section: Discussioncontrasting

confidence: 99%

LHCGR Gene Analysis in Girls with Non-Classic Central Precocious Puberty

Jeong

Lee

Hwang

2018

Exp Clin Endocrinol Diabetes

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Section: Discussioncontrasting

confidence: 99%

LHCGR Gene Analysis in Girls with Non-Classic Central Precocious Puberty

Jeong

Lee

Hwang

2018

Exp Clin Endocrinol Diabetes

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“…The human LHCGR is a member of the G protein-coupled receptor family and consists of 11 exons and 10 introns with seven transmembrane helices, located on the short arm of chromosome 2 (2p21) ( 6 ). LHCGR gene mutations have been described in several populations such as Brazilian ( 6 ), American ( 7 ), and Japanese ( 8 ). A total of 16 mutations had been reported (limited missense variants).…”

Section: Discussionmentioning

confidence: 99%

“…Activating mutations identified in boys with FMPP are mostly located in exon 11, resulting in LHCGR highly expressed in testicular Leydig cells, with resultant excessive testosterone production ( 9 ). The restricted number of LHCGR gene mutations found in familial and sporadic cases strongly infer that only mutation in specific domains of the receptor can autonomously activate cAMP cell signaling ( 6 ). Furthermore, female patients who carry LHCGR-activating mutations do not present with clinical or hormonal abnormalities, indicating the lack of phenotypic expression of these mutations ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Long-Term Treatment With Letrozole in a Boy With Familial Male-Limited Precocious Puberty

et al. 2022

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BackgroundThe long-term follow-up in children with familial male-limited precocious puberty (FMPP) who were treated with letrozole, triptorelin, and spironolactone is limited, especially considering the efficiency and safety.ObjectiveWe describe the clinical characteristics and long-term treatment with letrozole on adult height of a boy diagnosed with FMPP, confirmed by analysis of the LHCGR gene.MethodsPhysical examinations, bone age (BA), testosterone, and gonadotropin levels were measured as well as gene sequencing of the proband and parents.ResultsThe boy was referred to the hospital at 3.1 years of age due to peripheral precocious puberty. His height was 116.8cm (+5.1SD) and BA was 9 years. Genetic analysis revealed a patrilineal c.1703C>T.(p.Ala568Val) mutation of the LHCGR gene. After treating with letrozole for 1.6 years, the height according to BA went from -3.52SD to -2.82SD. Triptorelin was added at age 4.7 years based on both the evidence of central puberty and his growth velocity according to BA. During the 6.9 years of treatment, he had a height gain of 51.9cm, and BA increased 5.2 years. At age 10, his present height is 168.7cm (0.05SD) and BA is 14.7 years. No adverse effects of treatment were encountered.ConclusionA patrilineal mutation of the LHCGR gene has been identified in a boy with FMPP. His height is 168.7cm (-0.05SD) which is approaching his adult height after long-term treatment with letrozole, triptorelin, and spironolactone.

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“…The most common mutation reported in the literature is p.D578G [ 78 , 79 ]. Interestingly, at this position, other missense variants have been described: p.D578E [ 80 ], p.D578Y [ 81 ], D578V [ 82 ], and p.D578H. Remarkably, p.D578H is somatic in nature and associated with Leydig cell adenomas [ 78 , 83 ].…”

Section: Luteinizing Hormone Receptormentioning

confidence: 99%

Mitochondrial Dynamics as Potential Modulators of Hormonal Therapy Effectiveness in Males

Errico

Vinco

Ambrosini

et al. 2023

Biology

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Worldwide the incidence of andrological diseases is rising every year and, together with it, also the interest in them is increasing due to their strict association with disorders of the reproductive system, including impairment of male fertility, alterations of male hormones production, and/or sexual function. Prevention and early diagnosis of andrological dysfunctions have long been neglected, with the consequent increase in the incidence and prevalence of diseases otherwise easy to prevent and treat if diagnosed early. In this review, we report the latest evidence of the effect of andrological alterations on fertility potential in both young and adult patients, with a focus on the link between gonadotropins’ mechanism of action and mitochondria. Indeed, mitochondria are highly dynamic cellular organelles that undergo rapid morphological adaptations, conditioning a multitude of aspects, including their size, shape, number, transport, cellular distribution, and, consequently, their function. Since the first step of steroidogenesis takes place in these organelles, we consider that mitochondria dynamics might have a possible role in a plethora of signaling cascades, including testosterone production. In addition, we also hypothesize a central role of mitochondria fission boost on the decreased response to the commonly administrated hormonal therapy used to treat urological disease in pediatric and adolescent patients as well as infertile adults.

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Cosegregation of a novel mutation in the sixth transmembrane segment of the luteinizing/choriogonadotropin hormone receptor with two Brazilian siblings with severe testotoxicosis

Cited by 11 publications

References 29 publications

LHCGR Gene Analysis in Girls with Non-Classic Central Precocious Puberty

LHCGR Gene Analysis in Girls with Non-Classic Central Precocious Puberty

Long-Term Treatment With Letrozole in a Boy With Familial Male-Limited Precocious Puberty

Mitochondrial Dynamics as Potential Modulators of Hormonal Therapy Effectiveness in Males

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