ArticleEuropean journal of human genetics : EJHG2019
Heterozygous LHX3 mutations may lead to a mild phenotype of combined pituitary hormone deficiency.
Article in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- The molecular basis of hypoprolactinaemia.Reviews in endocrine & metabolic disorders · 2024Review
- Modeling corticotroph deficiency with pituitary organoids supports the functional role ofeLife · 2024Article
- Hearing impairment and vestibular function in patients with a pathogenic splice variant in the LHX3 gene.BMC medical genomics · 2024Article
- Polymorphism and association study of lactoferrin (LF) gene with milk yield, milk composition, and somatic cell count in Beetal goats.Tropical animal health and production · 2023Article
- Genetic Aspects of Small for Gestational Age Infants Using Targeted-Exome Sequencing and Whole-Exome Sequencing: A Single Center Study.Journal of clinical medicine · 2022Article
- The Genetic Backdrop of Hypogonadotropic Hypogonadism.International journal of molecular sciences · 2021Review
- Dwarfism in Tibetan Terrier dogs with anJournal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2021Article
- Comprehensive Identification of Pathogenic Gene Variants in Patients With Neuroendocrine Disorders.The Journal of clinical endocrinology and metabolism · 2021Article
- Whole Exome Sequencing Uncovered the Genetic Architecture of Growth Hormone Deficiency Patients.Frontiers in endocrinology · 2021Article
- Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic.Frontiers in genetics · 2021Article
- Rathke's cleft-like cysts arise from Isl1 deletion in murine pituitary progenitors.The Journal of clinical investigation · 2020Article
- Congenital Hypopituitarism During the Neonatal Period: Epidemiology, Pathogenesis, Therapeutic Options, and Outcome.Frontiers in pediatrics · 2020Review
- Genetic causes of hypopituitarism.Archives of medical science : AMS · 2020Article
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Authors and funding
12 authors at 5 institutions in 3 countries.
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Abstract
LHX3 is an LIM domain transcription factor involved in the early steps of pituitary ontogenesis. We report here functional studies of three allelic variants, including the first heterozygous variant of LHX3 NM_178138.5(LHX3):c.587T>C (p.(Leu196Pro)) that may be responsible for a milder phenotype of hypopituitarism. Our functional studies showed that NM_178138.5(LHX3):c.587T>C (p.(Leu196Pro)) was not able to activate target promoters in vitro, as it did not bind DNA, and likely affected LHX3 function via a mechanism of haplo-insufficiency. Our study demonstrates the possibility that patients with a heterozygous variant of LHX3 may have pituitary deficiencies, with a milder phenotype than patients with homozygous variants. It is thus of vital to propose an optimal follow-up of such patients, who, until now, were considered as not being at risk of presenting pituitary deficiency. The second variant NM_178138.5(LHX3):c.622C>G (p.(Arg208Gly)), present in a homozygous state, displayed decreased transactivating ability without loss of binding capacity in vitro, concordant with in silico analysis; it should thus be considered to affect LHX3 function. In contrast, the NM_178138.5(LHX3):c.929G>C (p.(Arg310Pro)) variant, in a heterozygous state, also predicted as deleterious in silico, proved functionally active in vitro, and should thus still be classified as a variant of unknown significance. Our study emphasizes the need for functional studies due to the limits of software-based predictions of new variants, and the possible association of a pituitary phenotype to heterozygous LHX3 variants.
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