Truncating RAX Mutations: Anophthalmia, Hypopituitarism, Diabetes Insipidus, and Cleft Palate in Mice and Men

The Journal of Clinical Endocrinology and Metabolism
Cécile BrachetPeter H Mathers

Abstract

The transcription factor RAX is a paired-type homeoprotein that plays a critical role in eye and forebrain development of vertebrate species. RAX knockout mice have anophthalmia, cleft palate, and an abnormal hypothalamus and display perinatal lethality. In humans, homozygous or compound heterozygous RAX mutations have been reported to cause bilateral microphthalmia or anophthalmia without consistent associated features. Congenital hypopituitarism can be associated with various eye or craniofacial anomalies; however, the co-occurrence of congenital hypopituitarism, anophthalmia, cleft palate, and diabetes insipidus has been very rare. We report the case of a child with anophthalmia, congenital hypopituitarism, diabetes insipidus, and bilateral cleft lip and palate who had a homozygous frameshift truncating mutation c.266delC (p.Pro89Argfs*114) in exon 1 of the RAX gene. Rax knockout mice show loss of ventral forebrain structures, pituitary, and basosphenoid bone and palate and a misplaced anterior pituitary gland along the roof of the oral cavity. Our patient's phenotype was more severe than that reported in other patients. Although most of the previously reported patients with RAX mutations showed either a missense or some les...Continue Reading

References

Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·T FurukawaC L Cepko
Oct 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Erich RoesslerMaximilian Muenke
Dec 10, 2003·Human Molecular Genetics·Vera A VoroninaPeter H Mathers
Apr 21, 2005·Human Mutation·Marie-Laure SobrierSerge Amselem
Jul 13, 2006·American Journal of Medical Genetics. Part a·Leisha D NolenRobyn V Jamieson
Apr 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Hiroki DannoMakoto Asashima
Sep 12, 2008·Clinical Genetics·L LequeuxP Calvas
Jul 14, 2011·Journal of Neurochemistry·Kristian RohdeMartin F Rath
Apr 25, 2012·Development, Growth & Differentiation·Yuki MuranishiTakahisa Furukawa
May 27, 2014·European Journal of Medical Genetics·Kathleen A Williamson, David R FitzPatrick
Oct 25, 2014·European Journal of Endocrinology·Masaki TakagiTomonobu Hasegawa

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Citations

Nov 9, 2019·The Journal of Clinical Endocrinology and Metabolism·Louise Cheryl Gregory, Mehul Tulsidas Dattani
Oct 22, 2020·Indian Journal of Endocrinology and Metabolism·Julie Elizabeth MathewSanjay Kalra
Aug 22, 2021·Nature Reviews. Endocrinology·Camille HageRoberto Salvatori

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