Sporadic Heterozygous Frameshift Mutation ofHESX1Causing Pituitary and Optic Nerve Hypoplasia and Combined Pituitary Hormone Deficiency in a Japanese Patient

• DOI: 10.1210/jc.2002-020818
• Publication Date: 2003-01-08T17:42:41Z
• Authors: Toshihiro Tajima; Tsukasa Hattorri; Takeo Nakajima; Kouji Okuhara; Kohei Sato; Shuji Abe; Jun Nakae; Kenji Fujieda
• Keywords: Optic nerve hypoplasia

HESX1/Hesx1 is a member of the paired-like class homeobox genes and essential for pituitary forebrain development. Mice with targeted homozygous deletion Hesx1 show severe central nervous system defects, absence optic vesicles, very small anterior gland. This phenotype similar to abnormalities observed in human disorder called septo-optic dysplasia, syndromic form congenital hypopituitarism. To date, four missense mutations HESX1 have been described individuals phenotypes ranging from relatively mild combined hormone deficiency (CPHD), isolated GH deficiency. Here we report Japanese patient CPHD (GH, TSH, LH, FSH, ACTH deficiency) due novel sporadic mutation. Brain magnetic resonance imaging examination revealed hypoplastic pituitary, ectopic posterior lobe, left nerve hypoplasia. Molecular analysis identified insertion heterozygous mutation (306/307ins AG) exon 2 HESX1. changes reading frame introduces premature stop codon soon after site. Therefore, this would be predicted generate protein lacking carboxyl-terminal homebox domain (DNA-binding domain) cause disease. Family demonstrated that neither patient's parents harbored mutation, indicating had arisen de novo. In conclusion, novo frameshift causes hypoplasia human.