A Novel Mutation (V101A) of the LHX4 Gene in a Japanese Patient with Combined Pituitary Hormone Deficiency

Objective LHX4, a LIM-homeodomain transcription factor, is required for development of the pituitary and nervous system. Several mutations of the LHX4 gene have been identified in patients with combined pituitary hormone deficiency (CPHD). The objective of the study was to clarify the molecular basis of a Japanese patient of CPHD with a small anterior pituitary and an ectopic posterior pituitary. Methods Genomic DNA was extracted from blood samples of the patient. Exons and exon-intron junctions of the LHX4 gene were amplified and sequenced. An expression vector of the mutant LHX4 protein was constructed and its function was analyzed in vitro. Results A novel missense mutation (V101A) was identified. In vitro transfection studies demonstrated that V101A mutant LHX4 was unable to activate the POU1F1 and FSH beta subunit gene promoter, indicating a loss of function mutation. Conclusion Our results identify a novel loss of function mutation of the LHX4 gene in a Japanese patient with CPHD.