In this study, 97 unrelated patients with the loss of more than one pituitary hormone were screened for mutations in the LHX4 gene. From this screening, two brothers were identified with a missense mutation on both copies of this gene, termed ‘homozygous’ mutations. Sequencing of the unaffected parents’ DNA showed that they both only carried one copy of the mutation, suggesting that one copy of the mutation was inherited from each parent. Despite early intervention with hormone therapy, both boys died within one week of birth.
LHX4 encodes a member of the LIM-homeodomain family of transcription factors that is required for normal development of the pituitary gland. To date, mutations in ;LHX4 have only been described in patients carrying a mutation on one allele, resulting in varying loss of pituitary hormones. This is the first report describing a homozygous LHX4 variant in a patient. The authors propose that impaired protein formation, such as decreased binding of LHX4 to its protein partners, may be a possible mechanism that leads to this lethal condition.
These findings were published by Professor Mehul Dattani in the Journal of Clinical Endocrinology and Metabolism. Professor Dattani is a BRC-supported investigator and Louise Gregory (the lead author on the publication) is a recipient of the 2015 BRC Doctoral Support Fund.