Background: Pituitary hormone deficiency combined type 3 (CPHD3; MIM# 221750) is an autosomal recessive combined pituitary hormone deficiency caused by mutations in LHX3, a LIM-homeodomain transcription factor gene which is necessary for the normal pituitary and motorneuron development.
Aims: Clinical manifestations of CPHD3 are pituitary dwarfism and might be accompanied by rigid cervical spine leading to limited neck rotation or sensorineural deafness. In this study, three patients from two unrelated consanguineous families of Saudi origin with combined pituitary hormone deficiency were examined.
Results: Clinical evaluation revealed that all the three patients had severe combined pituitary hormone deficiency, short neck and sensorineural hearing loss. The patient displayed a severe pituitary hypoplasia, whereas one patient also presented secondarily with an enlarged anterior pituitary. We identified one novel missense LHX3 mutation (p.C146F) in the LIM2 domain at a phylogenetically conserved residue, and a novel nonsense mutation (p.R156*) predicting a severely truncated protein, both in the homozygous form.
Conclusion: This report describes the first LHX3 mutations from Saudi patients and also expands the allelic spectrum for this gene and helps in the differential diagnosis.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology