Endocrine Abstracts

Background: Disturbances of pubertal timing affect >4% of the population and are associated with adverse health outcomes. Studies estimate 60–80% of variation in pubertal onset is genetically determined, but few genetic factors are known. We hypothesise that causal variants will be low-frequency, intermediate-impact variants and will be enriched in populations at the extremes of normal pubertal timing. Families with constitutional delay in growth and puberty (CDGP) ha...

Background: Pubertal timing has importance both for the individual, but also for public health. Previous studies estimate that 60–80% of variation in pubertal onset is genetically determined. Recently, a large genome-wide association study (GWAS) meta-analysis identified 42 loci for age-at-menarche (AAM), which explained 3.6–6.1% of the variation in the general population, but causal genes have not been identified.CDGP is defined as pubertal on...

Background: Self-limited delayed puberty (DP) often segregates in an autosomal dominant pattern, suggesting that inheritance is conferred by a small number of genes. However, the underlying genetic background is mostly unknown. By comparison, many genes have been identified where loss-of-function mutations lead to hypogonadotropic hypogonadism (HH). Despite likely overlap between the pathophysiology of delayed puberty and conditions of GnRH deficiency, few studies have examine...

Background: Disturbances of pubertal timing affect >4% of the population and are associated with adverse health outcomes. Studies estimate 60–80% of variation in pubertal onset is genetically determined, but few genetic factors are known. We hypothesise that causal variants will be low-frequency, intermediate-impact variants and will be enriched in populations at the extremes of normal pubertal timing. Families with constitutional delay in growth and puberty (CDGP) ha...

Background: The initiation of puberty is heralded by increasing gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. During embryonic life the GnRH neuroendocrine network develops thanks to a coordinated migration of neurons from the nasal placode to the forebrain. Our group has previously demonstrated that dysregulation in GnRH neuronal migration leads to delayed pubertal onset. Late puberty affects up to 2% of the population and is associated with adverse h...

Background: Self-limited DP often segregates in an autosomal dominant pattern, but in the majority of patients the neuroendocrine pathophysiology and its genetic regulation remain unclear. By comparison, many genes have been identified where loss-of-function mutations lead to IHH. Despite likely overlap between the pathophysiology of DP and conditions of GnRH deficiency, few studies have examined the contribution of mutations in IHH genes to the phenotype of DP.<p class="a...

Background: Abnormal pubertal timing affects over 4% of adolescents and is associated with adverse health and psychosocial outcomes. Previous studies estimate that 60–80% of variation in the timing of pubertal onset is genetically determined. However, despite this strong heritability, little is known about the genetic control of human puberty. Self-limited delayed puberty (DP) segregates in an autosomal dominant pattern, but in the majority of patients the neuroendocrine ...

Background: Timing of puberty is associated with height, cardiovascular health and cancer risk, with a significant public health impact. Previous studies estimate that 60–80% of variation in the timing of pubertal onset is genetically determined. Self-limited delayed puberty (DP) segregates in an autosomal dominant pattern, but the underlying genetic background is unknown.Methods: We performed whole exome sequencing in 111 members of 18 families fro...