Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
ARNT2 mutation causes hypopituitarism, post-natal microcephaly, visual and renal anomalies
Brain, Volume 136, No. 10, Year 2013
Notification
URL copied to clipboard!
Description
We describe a previously unreported syndrome characterized by secondary (post-natal) microcephaly with fronto-temporal lobe hypoplasia, multiple pituitary hormone deficiency, seizures, severe visual impairment and abnormalities of the kidneys and urinary tract in a highly consanguineous family with six affected children. Homozygosity mapping and exome sequencing revealed a novel homozygous frameshift mutation in the basic helix-loop-helix transcription factor gene ARNT2 (c.1373-1374dupTC) in affected individuals. This mutation results in absence of detectable levels of ARNT2 transcript and protein from patient fibroblasts compared with controls, consistent with nonsense-mediated decay of the mutant transcript and loss of ARNT2 function. We also show expression of ARNT2 within the central nervous system, including the hypothalamus, as well as the renal tract during human embryonic development. The progressive neurological abnormalities, congenital hypopituitarism and post-retinal visual pathway dysfunction in affected individuals demonstrates for the first time the essential role of ARNT2 in the development of the hypothalamo-pituitary axis, post-natal brain growth, and visual and renal function in humans. © 2013 The Author (2013). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
Authors & Co-Authors
Webb, Emma A.
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Al-Mutair, Angham Nasser
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Kelberman, Daniel
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Bacchelli, Chiara
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Lescai, Francesco
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Andoniadou, Cynthia Lilian
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Banyan, Abdul
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Alsawaid, Al
Saudi Arabia, Riyadh
King Abdulaziz Medical City - Riyadh
Alrifai, Muhammad Talal
Saudi Arabia, Riyadh
King Abdulaziz Medical City - Riyadh
Alahmesh, Mohammed A.
Saudi Arabia, Riyadh
Alfaisal University
Balwi, Mohammed Al
Saudi Arabia, Riyadh
King Abdulaziz Medical City - Riyadh
Neda Mousavy-Gharavy, Seyedeh
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Lukovic, Biljana
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Burke, Derek G.
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
McCabe, Mark James
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Kasia, Tessa
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Kleta, Robert
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Stupka, Elia
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Italy, Milan
Irccs Ospedale San Raffaele
Beales, Philip L.Philip L.
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Thompson, Dorothy A.
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Chong, Wui ‘Kling’
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Alkuraya., Fowzan S.
Saudi Arabia, Riyadh
Alfaisal University
Martínez-Barbera, Juan Pedro
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Sowden, Jane C.
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Dattani, Mehul Tulsidas
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Statistics
Citations: 66
Authors: 25
Affiliations: 6
Identifiers
Doi:
10.1093/brain/awt218
e-ISSN:
14602156
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Maternal And Child Health