A Novel Missense Mutation (P366T) of the LHX4 Gene Causes Severe Combined Pituitary Hormone Deficiency with Pituitary Hypoplasia, Ectopic Posterior Lobe and a Poorly Developed Sella Turcica

• Published in: Endocrine Journal Vol. 54; no. 4; pp. 637 - 641
• Main Authors: TAJIMA, Toshihiro, HATTORI, Tsukasa, NAKAJIMA, Takeo, OKUHARA, Koji, TSUBAKI, Junko, FUJIEDA, Kenji
• Format: Journal Article
• Language: English
• Published: Japan The Japan Endocrine Society 2007
• Subjects: Combined pituitary hormone deficiency (CPHD); Female; Homeodomain Proteins - genetics; Humans; Hypopituitarism - congenital; Hypopituitarism - genetics; Hypopituitarism - pathology; Infant; LHX4; LIM-Homeodomain Proteins; Magnetic Resonance Imaging; Mutation, Missense; Occipital Lobe - abnormalities; Occipital Lobe - pathology; Pituitary Gland, Anterior - abnormalities; Pituitary Gland, Anterior - pathology; Pituitary Hormones - deficiency; Pituitary hypoplasia; Sella turcica; Sella Turcica - abnormalities; Sella Turcica - pathology; Severity of Illness Index; Transcription Factors - genetics
• ISSN: 0918-8959; 1348-4540
• DOI: 10.1507/endocrj.K06-200

LIM homeodomain transcription factors regulate many aspects of development in multicellular organisms. LHX4/Lhx4 is a protein that is essential for pituitary development and motor neuron specification in mammals. In human, a heterozygous splicing mutation of the LHX4 gene was reported in a family with combined pituitary hormone deficiencies (CPHD). In addition to CPHD, these patients were characterized by small sella turcica and chiari malformation. Here we report a Japanese patient with CPHD (GH, PRL, TSH, LH, FSH, and ACTH deficiency) due to a novel missense mutation (P366T) of the LHX 4 gene. She showed severe respiratory disease and hypoglycemia soon after birth. Brain MRI demonstrated hypoplastic anterior pituitary, ectopic posterior lobe, a poorly developed sella turcica, and chiari malformation. Sequence analysis of the LHX 4 gene identified a heterozygous missense mutation (P366T) in exon 6, which was present in LIM4 specific domain. Neither of the patient's parents harbored this mutation, indicating de novo mutation.