hrp0094fc8.1 | Neuroendocrinology | ESPE2021

Combined omic analysis revealed autism-linked NLGN3 as new candidate gene associated to GnRH neuron development and disease.

Oleari Roberto , Lettieri Antonella , Paganoni Alyssa , Howard Sasha R , Cariboni Anna ,

During development, gonadotropin releasing hormone (GnRH) neurons are born in the nasal placode and migrate to the hypothalamus, where they position to regulate sexual reproduction by pulsatile release of GnRH. Defective GnRH neuron development or action may lead to GnRH deficiency (GD) which is characterized by absent or delayed puberty. Several GD causative genes have been identified so far, but half of the cases are still idiopathic. The employment of complementary research...

hrp0097fc13.3 | Pituitary, neuroendocrinology and puberty 2 | ESPE2023

Variants in Methyl-CpG-binding protein 2 (MECP2) are associated with X-Linked Central Precocious Puberty

E Read Jordan , Guasti Leonardo , Paganoni Alyssa , Korbonits Marta , R Howard Sasha

Whilst several key genetic contributors to the phenotype of central precocious puberty (CPP) have been recognized, many familial cases remain without clear a genetic aetiology. Causal genetic variants are reported in imprinted genes Makorin ring finger protein 3 (MKRN3) and Delta-like homolog 1 (DLK1), alongside Kisspeptin-1 (KISS1) and (KISSR1), implicating mis-regulation of transcriptional control of the kisspeptin and GnRH neuroendocrine systems in onset of CPP. We recently...

hrp0097s12.2 | What's new for the HPG Axis | ESPE2023

SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability

Cariboni Anna , Oleari Roberto , Lettieri Antonella , van den Munkhof Marleen , van Battum Eljo , Tacconi Carlotta , Spreafico Marco , Paganoni Alyssa , Amoruso Federica , Eberini Ivano , Dunkel Leonard , Fantin Alessandro , Howard Sasha , Pasterkamp Jeroen

Innervation of the hypothalamic median eminence by Gonadotropin-Releasing Hormone (GnRH) neurons is vital to ensure puberty onset and successful reproduction. However, the molecular and cellular mechanisms underlying median eminence development and pubertal timing are incompletely understood. Here we show that Semaphorin-6A is strongly expressed by median eminence-resident oligodendrocytes positioned adjacent to GnRH neuron projections and fenestrated capillaries, and that Sem...

hrp0095p1-545 | Pituitary, Neuroendocrinology and Puberty | ESPE2022

X-Linked Central Precocious Puberty Associated with MECP2 defects

Canton Ana , Tinano Flavia , Guasti Leonardo , Montenegro Luciana , Ryan Fiona , Shears Deborah , Edna Melo Maria , Gomes Larissa , Piana Mariana , Brauner Raja , Espino Rafael , Escribano-Muñoz Arancha , Paganoni Alyssa , Korbonits Marta , Eduardo Seraphim Carlos , Faria Aline , Costa Silvia , Cristina Krepischi Ana , Jorge Alexander , David Alessia , Argente Jesús , Mendonca Berenice , Brito Vinicius , Howard Sasha , Claudia Latronico Ana

Background: Genetic causes of central precocious puberty (CPP) has been increasingly recognized, extending our knowledge of the triggering factors of human pubertal timing. Distinct etiologies remain to be elucidated in sporadic and familial cases. Methyl-CpG-binding protein 2 (MECP2) is a chromatin-associated protein that can activate or repress gene transcription, playing a role in neuronal maturation. It is encoded by MECP2 gene located at chromoso...

hrp0094fc8.2 | Neuroendocrinology | ESPE2021

Recessive PRDM13 mutations result in hypogonadotropic hypogonadism and cerebellar hypoplasia

Gregory Louise C. , Whittaker Danielle E , Oleari Roberto , Quesne-Stabej Polona Le , Williams Hywel J. , UCL GOSgene , Torpiano John G , Formosa Nancy , Cachia Mario J. , Field Daniel , Lettieri Antonella , Ocaka Louise , De Martini Lisa Benedetta , Rajabali Sakina , Riegman Kimberley L. , Paganoni Alyssa J.J. , Chaya Taro , Robinson Iain C.A.F. , Furukawa Takahisa , Cariboni Anna , Basson M. Albert , Dattani Mehul T. ,

Three patients from two unrelated families in Malta; one consanguineous (siblings: Patient 1, male and Patient 2, female) and one non-consanguineous (Patient 3, male), manifested hypogonadotropic hypogonadism with delayed puberty, intellectual disability, scoliosis, and ataxia with cerebellar hypoplasia on MRI. GnRH tests revealed low peak LH and FSH concentrations in the patients: Patient 1; LH 2.3 IU/L, FSH 4.4 IU/L (14.3y), Patient 2; LH 3.6 IU/L, FSH 6.4 IU/L (12.5y), Pati...