Bassam Bin-Abbas1, Doha Al-Humaida1, Afaf Al-Sagheir1, Ebtesam Qasem2, Mai Almohanna2, Ali S Alzahrani3. 1. Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. 2. Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. 3. Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Abstract
OBJECTIVE: To describe conflicting gender identities in three karyotypically female siblings with congenital adrenal hyperplasia (CAH) caused by a novel mutation in the CYP11B1 gene, who were assigned as males at birth and followed up to adulthood. METHODS: We present 3 siblings (16, 14 and 10 years old) who were born with severe genital virilization and raised as males. Clinical examination showed Prader IV to V external genitalia with a stretched penile length of 7 to 11 cm. Adrenocorticotrophic hormone (ACTH) stimulation test showed a stimulated 11 deoxycortisol (11DOC) level of 12,300-18,700 μg/L (normal 0-5 μg/L). Their karyotypes were 46 XX, and they had normal-sized uterus and ovaries on pelvic ultrasound. DNA was isolated from peripheral leukocytes, and polymerase chain reaction (PCR) and direct sequencing revealed a novel CYP11B1 mutation. This mutation leads to a c.53_54 T insertion (c.53_54insT) with frameshift and truncation at c.115 (codon 39) of CYP11B1. RESULTS: Psychological evaluation of the oldest sibling suggested a female gender identity, and she declared herself as female, and female sex was re-assigned after 1 year of psychosocial adjustment. Psychological assessment for the 2 younger siblings and a fourth 46XY sibling with the same condition revealed male gender identities, and they continued their lives as males without significant difficulties. CONCLUSION: Divergent gender identity was observed in three severely masculinized 46XX siblings with CAH who carried the same CYP11B1 mutation and had comparable postnatal and probably prenatal androgen exposure and environmental circumstances. These cases suggest that the basis of gender identity is more complex than chromosomal, biochemical, and genetic constitution.
OBJECTIVE: To describe conflicting gender identities in three karyotypically female siblings with congenital adrenal hyperplasia (CAH) caused by a novel mutation in the CYP11B1 gene, who were assigned as males at birth and followed up to adulthood. METHODS: We present 3 siblings (16, 14 and 10 years old) who were born with severe genital virilization and raised as males. Clinical examination showed Prader IV to V external genitalia with a stretched penile length of 7 to 11 cm. Adrenocorticotrophic hormone (ACTH) stimulation test showed a stimulated 11 deoxycortisol (11DOC) level of 12,300-18,700 μg/L (normal 0-5 μg/L). Their karyotypes were 46 XX, and they had normal-sized uterus and ovaries on pelvic ultrasound. DNA was isolated from peripheral leukocytes, and polymerase chain reaction (PCR) and direct sequencing revealed a novel CYP11B1 mutation. This mutation leads to a c.53_54 T insertion (c.53_54insT) with frameshift and truncation at c.115 (codon 39) of CYP11B1. RESULTS: Psychological evaluation of the oldest sibling suggested a female gender identity, and she declared herself as female, and female sex was re-assigned after 1 year of psychosocial adjustment. Psychological assessment for the 2 younger siblings and a fourth 46XY sibling with the same condition revealed male gender identities, and they continued their lives as males without significant difficulties. CONCLUSION: Divergent gender identity was observed in three severely masculinized 46XX siblings with CAH who carried the same CYP11B1 mutation and had comparable postnatal and probably prenatal androgen exposure and environmental circumstances. These cases suggest that the basis of gender identity is more complex than chromosomal, biochemical, and genetic constitution.
Authors: Ahmed Khattab; Shozeb Haider; Ameet Kumar; Samarth Dhawan; Dauood Alam; Raquel Romero; James Burns; Di Li; Jessica Estatico; Simran Rahi; Saleel Fatima; Ali Alzahrani; Mona Hafez; Noha Musa; Maryam Razzghy Azar; Najoua Khaloul; Moez Gribaa; Ali Saad; Ilhem Ben Charfeddine; Berenice Bilharinho de Mendonça; Alicia Belgorosky; Katja Dumic; Miroslav Dumic; Javier Aisenberg; Nurgun Kandemir; Ayfer Alikasifoglu; Alev Ozon; Nazli Gonc; Tina Cheng; Ursula Kuhnle-Krahl; Marco Cappa; Paul-Martin Holterhus; Munier A Nour; Daniele Pacaud; Assaf Holtzman; Sun Li; Mone Zaidi; Tony Yuen; Maria I New Journal: Proc Natl Acad Sci U S A Date: 2017-02-22 Impact factor: 11.205
Authors: Adnan Al Shaikh; Yasser AlGhanmi; Saniah Awidah; Abdullah Bahha; Mohamed E Ahmed; Ashraf T Soliman Journal: Indian J Endocrinol Metab Date: 2019 May-Jun