@article{Canton:2023:10.1016/s2213-8587(23)00131-6,
author = {Canton, APM and Tinano, FR and Guasti, L and Montenegro, LR and Ryan, F and Shears, D and de, Melo ME and Gomes, LG and Piana, MP and Brauner, R and Espino-Aguilar, R and Escribano-Muñoz, A and Paganoni, A and Read, JE and Korbonits, M and Seraphim, CE and Costa, SS and Krepischi, AC and Jorge, AAL and David, A and Kaisinger, LR and Ong, KK and Perry, JRB and Abreu, AP and Kaiser, UB and Argente, J and Mendonca, BB and Brito, VN and Howard, SR and Latronico, AC},
doi = {10.1016/s2213-8587(23)00131-6},
journal = {The Lancet Diabetes & Endocrinology},
pages = {545--554},
title = {Rare variants in the MECP2 gene in girls with central precocious puberty: a translational cohort study},
url = {http://dx.doi.org/10.1016/s2213-8587(23)00131-6},
volume = {11},
year = {2023}
}

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TY  - JOUR
AB  - BackgroundIdentification of genetic causes of central precocious puberty have revealed epigenetic mechanisms as regulators of human pubertal timing. MECP2, an X-linked gene, encodes a chromatin-associated protein with a role in gene transcription. MECP2 loss-of-function mutations usually cause Rett syndrome, a severe neurodevelopmental disorder. Early pubertal development has been shown in several patients with Rett syndrome. The aim of this study was to explore whether MECP2 variants are associated with an idiopathic central precocious puberty phenotype.MethodsIn this translational cohort study, participants were recruited from seven tertiary centres from five countries (Brazil, Spain, France, the USA, and the UK). Patients with idiopathic central precocious puberty were investigated for rare potentially damaging variants in the MECP2 gene, to assess whether MECP2 might contribute to the cause of central precocious puberty. Inclusion criteria were the development of progressive pubertal signs (Tanner stage 2) before the age of 8 years in girls and 9 years in boys and basal or GnRH-stimulated LH pubertal concentrations. Exclusion criteria were the diagnosis of peripheral precocious puberty and the presence of any recognised cause of central precocious puberty (CNS lesions, known monogenic causes, genetic syndromes, or early exposure to sex steroids). All patients included were followed up at the outpatient clinics of participating academic centres. We used high-throughput sequencing in 133 patients and Sanger sequencing of MECP2 in an additional 271 patients. Hypothalamic expression of Mecp2 and colocalisation with GnRH neurons were determined in mice to show expression of Mecp2 in key nuclei related to pubertal timing regulation.FindingsBetween Jun 15, 2020, and Jun 15, 2022, 404 patients with idiopathic central precocious puberty (383 [95%] girls and 21 [5%] boys; 261 [65%] sporadic cases and 143 [35%] familial cases from 134 unrelated families) were enrolled and
AU  - Canton,APM
AU  - Tinano,FR
AU  - Guasti,L
AU  - Montenegro,LR
AU  - Ryan,F
AU  - Shears,D
AU  - de,Melo ME
AU  - Gomes,LG
AU  - Piana,MP
AU  - Brauner,R
AU  - Espino-Aguilar,R
AU  - Escribano-Muñoz,A
AU  - Paganoni,A
AU  - Read,JE
AU  - Korbonits,M
AU  - Seraphim,CE
AU  - Costa,SS
AU  - Krepischi,AC
AU  - Jorge,AAL
AU  - David,A
AU  - Kaisinger,LR
AU  - Ong,KK
AU  - Perry,JRB
AU  - Abreu,AP
AU  - Kaiser,UB
AU  - Argente,J
AU  - Mendonca,BB
AU  - Brito,VN
AU  - Howard,SR
AU  - Latronico,AC
DO  - 10.1016/s2213-8587(23)00131-6
EP  - 554
PY  - 2023///
SN  - 2213-8587
SP  - 545
TI  - Rare variants in the MECP2 gene in girls with central precocious puberty: a translational cohort study
T2  - The Lancet Diabetes & Endocrinology
UR  - http://dx.doi.org/10.1016/s2213-8587(23)00131-6
UR  - http://hdl.handle.net/10044/1/105145
VL  - 11
ER  - 

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