A Novel LHX3 Variant Associated With Combined Pituitary Hormone Deficiency in an Indian Kindred.

Authors

Sreenivasan Palaniappan, Subbiah Sridhar, Senthilkumar Thasarathan, Dhivya Shanmugam, Pinaki Dutta

Published in

Cureus. Volume 18. Issue 6. Pages e111778. Epub Jun 29, 2026.

Abstract

LHX3, a LIM-homeodomain transcription factor, is crucial in pituitary development. Mutations of LHX3 are infrequently described in the Indian subcontinent. We report two siblings born of consanguineous marriage with combined pituitary hormone deficiency (CPHD) who presented with short stature and extra-pituitary skeletal abnormalities. Whole-exome sequencing (WES) of both siblings revealed an identical novel in-frame deletion variant in the LHX3 gene c.634_636del (p.Glu212del). Both parents of the patients were heterozygous carriers of the same LHX3 variant. The genetic sequencing data did not reveal any other potentially causal variants of other candidate genes that could be associated with CPHD. Furthermore, the conservation of the reference region across species and the expression of LHX3 in pituitary tissue provide additional evidence supporting its pathogenic role. This in-frame deletion, according to theoretical models, could potentially disrupt protein-protein interactions, DNA binding, and protein stability, ultimately disrupting the specification of pituitary cell types. Both patients exhibited a remarkable response to recombinant growth hormone therapy. This novel variant provides a foundation for future functional studies and contributes to the expanding genetic spectrum of LHX3 variants in CPHD.

PMID:
42534244
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.