ARNT2 mutation causes hypopituitarism, post-natal microcephaly, visual and renal anomalies.
Brain
; 136(Pt 10): 3096-105, 2013 Oct.
Article
en En
| MEDLINE
| ID: mdl-24022475
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hormonas Hipofisarias
/
Percepción Visual
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Translocador Nuclear del Receptor de Aril Hidrocarburo
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
/
Hipopituitarismo
/
Riñón
/
Microcefalia
/
Mutación
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
Límite:
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Brain
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido