hrp0094p1-50 | Sex Endocrinology and Gonads A | ESPE2021

Pathogenic variants in the human m6A reader YTHDC2 are associated with primary ovarian insufficiency

McGlacken-Byrne Sinead M , Torres Ignacio Del Valle , Stabej Polona Le Quesne , Belutti Laura , Ocaka Louise , Ishida Miho , Suntharalingham Jenifer P , Genomics UCL , Discovery GOSgene , Resource Human Developmental Biology , Dattani Mehul T , Kelberman Dan , Lagos Carlos F , Livera Gabriel , Conway Gerard S , Achermann John C ,

Background: Primary ovarian insufficiency (POI) is genetically mediated in up to 30% of cases. Many genes associated with POI have roles in early ovary developmental processes, including meiosis.Objectives: We investigated the genetic mechanism underlying early-onset POI in three young women presenting with absent puberty: two sisters from a consanguineous pedigree and a third unrelated proband.<st...

hrp0089fc9.3 | Pituitary, neuroendocrinology and Puberty 1 | ESPE2018

Mutations in MAGEL2 and L1CAM are Associated with Congenital Hypopituitarism and Arthrogryposis

Gregory Louise C , Pratik Shah , Sanner Juliane RF , Arancibia Monica , Hurst Jane , Jones Wendy D , Spoudeas Helen , Le Quesne Stabej Polona , Ocaka Louise , Loureiro Carolina , Martinez-Aguayo Alejandro , Williams Hywel , Dattani Mehul T

Background: Congenital hypopituitarism (CH), involving deficiencies in one or more anterior pituitary hormones, is rarely observed in combination with severe joint contractures, termed arthrogryposis. Schaaf-Yang syndrome (SHFYNG), which has phenotypic overlap with Prader-Willi syndrome, may be associated with arthrogryposis. L1 syndrome, a group of X-linked disorders including hydrocephalus and spasticity of the lower limbs, may also present with generalized contractures in r...

hrp0094p2-406 | Sex differentiation, gonads and gynaecology or sex endocrinology | ESPE2021

ZSWIM7 is associated with human female meiosis and familial primary ovarian insufficiency

McGlacken-Byrne Sinéad M , Le Quesne Stabej Polona , Del Valle Torres Ignacio , Ocaka Louise , Gagunashvili Andrey , Crespo Berta , Moreno Nadjeda , James Chela , Bacchelli Chiara , Dattani Mehul , Williams Hywel J , Kelberman Dan , Achermann John C , Conway Gerard S

Background: Primary ovarian insufficiency (POI) affects 1% of women and is associated with significant medical consequences. In approximately 10% of cases, POI presents early with absent puberty or primary amenorrhoea. A genetic cause for POI can be found in up to 30% of women. Identified genes often relate to the complex biological processes occurring in fetal life which underpin normal ovary development and function in later adulthood.Objective: We aim...

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...

hrp0092rfc15.1 | Late Breaking Abstracts | ESPE2019

Preclinical Studies of Acrodysostosis Gene AAV Therapy in a Knock-In R368X PRKAR1A Mouse Model

Le Stunff Catherine , Gunes Yasemin , Mille Clémence , Bougnères Pierre

The use of recombinant adeno-associated viruses (rAAV) as safe vectors have allowed hundreds of gene therapy attempts to treat monogenic diseases not including bone genetic diseases (Gao G, Nat Rev Drug Dis 2019). To our knowledge, there has been few attempts to apply gene therapy to monogenic bone diseases, largely because most skeletal malformations are being developed during fetal life. Patients affected with acrodysostosis are known to aggravate their skeletal malformation...

hrp0084p3-1011 | Growth | ESPE2015

Targeted Birth Length and Parental Height Measurement in Babies with Birthweight≤9th Centile; Improved Uptake During Second Study During 1 Calendar Year in a Single Newborn Unit

Sardar Colette Montgomery , Donnelly Sharon , Siddique Jamila , Gault Emma Jane , Kinmond Sheena , Donaldson Malcolm

Background: The contribution of intrauterine growth restriction (IUGR) and parental height (PH) to childhood short stature is difficult to determine in countries, including the UK, where birth length (BL) is not routinely measured, while accurate PH may become unavailable due to separation/divorce. A previous study (2008–2009) examined the feasibility of BL and PH measurement in the lightest 9% of babies born in a single maternity unit. Uptake was disappointing, with part...

hrp0086fc2.1 | Bone &amp; Mineral Metabolism | ESPE2016

Characterization of GNAS miRNAs Targets: Trying to Better Understand the Pathophysiology of Pseudohypoparathyroidism 1B (PHP1B)

Hanna Patrick , Netchine Irene , Le Stunff Catherine , Linglart Agnes

Background: Patients affected with PHP1B are characterized by resistance to PTH which binds to the PTH receptor and activate the cAMP/Gsa signaling pathway. Gsa is encoded by GNAS, a locus subjected to genomic imprinting. PHP1B patients present with abnormal methylation at the maternal A/B promoter and, in some cases, at the other promoters (XLas, GNAS-AS1 and NESP55) of the GNAS locus, likely leading to a decreased express...

hrp0086fc14.2 | Growth : Mechanisms | ESPE2016

CG Methylation at the IGF1 P2 Promoter is a Major Epigenetic Determinant of Postnatal, Not Foetal Growth

Ouni Myriam , Le Stunff Catherine , Castell Anne Laure , Bougneres Pierre

Background: The height of children has a Gaussian distribution. Genetics explain an important part of individual variability, but no single genomic variant accounts for more than 0.3% of height variance. At the interface of genetics and environment, epigenetics is expected to contribute to phenotypic variability. IGF1 is an attractive locus to test this hypothesis.Objectives: To quantify the effect of CG methylation of IGF1 promoters on height.<p cla...

hrp0094fc9.2 | Growth Hormone and IGFs | ESPE2021

A simple model with height and age at start of treatment with recombinant human growth hormone can accurately predict future growth in children with growth disorders

van Dommelen Paula , Arnaud Lilian , Masne Quentin Le , Koledova Ekaterina ,

Background: A growth prediction model would not only allow patients with growth disorders the opportunity to see the expected effect of their recombinant human growth hormone (r hGH) treatment, but also support healthcare professionals to individualise treatment to optimise growth outcomes.Aim: To develop a growth prediction model in children with growth disorders.Patients and Methods: Height and c...

hrp0094p1-131 | Growth Hormone and IGFs A | ESPE2021

The impact of lockdown regulations caused by the COVID-19 pandemic on adherence to recombinant human growth hormone therapy: Evidence from real-world data

van Dommelen Paula , Arnaud Lilian , Masne Quentin Le , Koledova Ekaterina ,

Background: We hypothesised that, due to the COVID-19 lockdown regulations, patients are at home more often and may, therefore, more diligently administer their growth hormone (GH) injections on a regular basis.Aim: To investigate the impact of COVID-19 lockdown regulations on adherence to recombinant human GH (r-hGH) therapy in patients with growth disorders, using real-world data.Patients and Met...