hrp0092fc11.1 | Pituitary, Neuroendocrinology and Puberty Session 2 | ESPE2019

Phenotypic Characterization of a Large Pediatric Cohort of Patients with Genetic Forms of Congenital Hypopituitarism

Cionna Cecilia , Cerbone Manuela , Gregory Louise C , Dattani Mehul T

Background: Genetic variants are identified in a small proportion (~10%) of patients with Congenital Hypopituitarism (CH), with variable associated phenotypes. We aimed to phenotypically characterise a large cohort of patients with genetically proven CH.Patients and methods: 1684 CH patients were screened (Sanger or whole exome sequencing) over a 20-year period (1998-2018) for mutations in genes regulating pitui...

hrp0086fc3.4 | Pituitary | ESPE2016

A Novel Mutation in Eukaryotic Translation Initiation Factor 2 Subunit 3 (EIF2S3) is Associated with X-Linked Hypopituitarism and Glucose Dysregulation

Gregory Louise C. , Williams Hywel , Rahman Sophia , Ferreira Carolina B. , Alatzoglou Kyriaki S. , Kapoor Ritika R. , Hussain Khalid , Gaston-Massuet Carles , Kelberman Daniel , Qasim Waseem , Dattani Mehul T.

Background: A mutation in EIF2S3 (NM_001415; Xp22.11) was previously associated with microcephaly and developmental delay in a single pedigree. EIF2S3 encodes the eukaryotic translation initiation factor 2 subunit 3 (eIF2γ), the largest of three EIF2 subunits. EIF2 initiates protein synthesis by forming a ternary complex with GTP and initiator methionyl-tRNA which then binds to the 40S ribosomal subunit, enabling scanning of mRNA from the 5′ end to...

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...

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...