A novel LHX3 mutation presenting as combined pituitary hormonal deficiency

Amrit P S Bhangoo, Chad S. Hunter, Jesse J. Savage, Henry Anhalt, Steven Pavlakis, Emily Walvoord, Svetlana Ten, Simon Rhodes

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Context: LHX3 encodes LIM homeodomain class transcription factors with important roles in pituitary and nervous system development. The only previous report of LHX3 mutations described patients with two types of recessive mutations displaying combined pituitary hormone deficiency coupled with neck rigidity. Objective: We report a patient presenting a unique phenotype associated with a novel mutation in the LHX3 gene. Patient: We report a 6-yr, 9-month-old boy born from a consanguineous relationship who presented shortly after birth with cyanosis, feeding difficulty, persistent jaundice, micropenis, and poor weight gain and growth rate. Laboratory data, including an undetectable TSH, low free T4, low IGF-I and IGF binding protein-3, prolactin deficiency, and LH and FSH deficiency were consistent with hypopituitarism. Arigid cervical spine leading to limited head rotation was noticed on follow-up examination. Magnetic resonance imaging revealed an apparently structurally normal cervical spine and a postcontrast hypointense lesion in the anterior pituitary. Results: Analysis of theLHX3gene revealed homozygosity for a novel single-base-pair deletion in exon 2. This mutation leads to a frame shift predicted to result in the production of short, inactive LHX3 proteins. The results of in vitro translation experiments are consistent with this prediction. The parents of the patients are heterozygotes, indicating a recessive mode of action for the deletion allele. Conclusions: The presence of a hypointense pituitary lesion and other clinical findings broadens the phenotype associated with LHX3 gene mutation.

Original languageEnglish
Pages (from-to)747-753
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number3
DOIs
StatePublished - Mar 2006

Fingerprint

Genes
Insulin-Like Growth Factor Binding Protein 3
Mutation
Pituitary Hormones
Neurology
Insulin-Like Growth Factor I
Rigidity
Prolactin
Magnetic resonance imaging
Exons
Transcription Factors
Spine
Phenotype
Hypopituitarism
Cyanosis
Heterozygote
Jaundice
Proteins
Base Pairing
Experiments

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

A novel LHX3 mutation presenting as combined pituitary hormonal deficiency. / Bhangoo, Amrit P S; Hunter, Chad S.; Savage, Jesse J.; Anhalt, Henry; Pavlakis, Steven; Walvoord, Emily; Ten, Svetlana; Rhodes, Simon.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 3, 03.2006, p. 747-753.

Research output: Contribution to journalArticle

Bhangoo, Amrit P S ; Hunter, Chad S. ; Savage, Jesse J. ; Anhalt, Henry ; Pavlakis, Steven ; Walvoord, Emily ; Ten, Svetlana ; Rhodes, Simon. / A novel LHX3 mutation presenting as combined pituitary hormonal deficiency. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 3. pp. 747-753.
@article{c9cef81a3fea45fda62390f985451a9f,
title = "A novel LHX3 mutation presenting as combined pituitary hormonal deficiency",
abstract = "Context: LHX3 encodes LIM homeodomain class transcription factors with important roles in pituitary and nervous system development. The only previous report of LHX3 mutations described patients with two types of recessive mutations displaying combined pituitary hormone deficiency coupled with neck rigidity. Objective: We report a patient presenting a unique phenotype associated with a novel mutation in the LHX3 gene. Patient: We report a 6-yr, 9-month-old boy born from a consanguineous relationship who presented shortly after birth with cyanosis, feeding difficulty, persistent jaundice, micropenis, and poor weight gain and growth rate. Laboratory data, including an undetectable TSH, low free T4, low IGF-I and IGF binding protein-3, prolactin deficiency, and LH and FSH deficiency were consistent with hypopituitarism. Arigid cervical spine leading to limited head rotation was noticed on follow-up examination. Magnetic resonance imaging revealed an apparently structurally normal cervical spine and a postcontrast hypointense lesion in the anterior pituitary. Results: Analysis of theLHX3gene revealed homozygosity for a novel single-base-pair deletion in exon 2. This mutation leads to a frame shift predicted to result in the production of short, inactive LHX3 proteins. The results of in vitro translation experiments are consistent with this prediction. The parents of the patients are heterozygotes, indicating a recessive mode of action for the deletion allele. Conclusions: The presence of a hypointense pituitary lesion and other clinical findings broadens the phenotype associated with LHX3 gene mutation.",
author = "Bhangoo, {Amrit P S} and Hunter, {Chad S.} and Savage, {Jesse J.} and Henry Anhalt and Steven Pavlakis and Emily Walvoord and Svetlana Ten and Simon Rhodes",
year = "2006",
month = "3",
doi = "10.1210/jc.2005-2360",
language = "English",
volume = "91",
pages = "747--753",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - A novel LHX3 mutation presenting as combined pituitary hormonal deficiency

AU - Bhangoo, Amrit P S

AU - Hunter, Chad S.

AU - Savage, Jesse J.

AU - Anhalt, Henry

AU - Pavlakis, Steven

AU - Walvoord, Emily

AU - Ten, Svetlana

AU - Rhodes, Simon

PY - 2006/3

Y1 - 2006/3

N2 - Context: LHX3 encodes LIM homeodomain class transcription factors with important roles in pituitary and nervous system development. The only previous report of LHX3 mutations described patients with two types of recessive mutations displaying combined pituitary hormone deficiency coupled with neck rigidity. Objective: We report a patient presenting a unique phenotype associated with a novel mutation in the LHX3 gene. Patient: We report a 6-yr, 9-month-old boy born from a consanguineous relationship who presented shortly after birth with cyanosis, feeding difficulty, persistent jaundice, micropenis, and poor weight gain and growth rate. Laboratory data, including an undetectable TSH, low free T4, low IGF-I and IGF binding protein-3, prolactin deficiency, and LH and FSH deficiency were consistent with hypopituitarism. Arigid cervical spine leading to limited head rotation was noticed on follow-up examination. Magnetic resonance imaging revealed an apparently structurally normal cervical spine and a postcontrast hypointense lesion in the anterior pituitary. Results: Analysis of theLHX3gene revealed homozygosity for a novel single-base-pair deletion in exon 2. This mutation leads to a frame shift predicted to result in the production of short, inactive LHX3 proteins. The results of in vitro translation experiments are consistent with this prediction. The parents of the patients are heterozygotes, indicating a recessive mode of action for the deletion allele. Conclusions: The presence of a hypointense pituitary lesion and other clinical findings broadens the phenotype associated with LHX3 gene mutation.

AB - Context: LHX3 encodes LIM homeodomain class transcription factors with important roles in pituitary and nervous system development. The only previous report of LHX3 mutations described patients with two types of recessive mutations displaying combined pituitary hormone deficiency coupled with neck rigidity. Objective: We report a patient presenting a unique phenotype associated with a novel mutation in the LHX3 gene. Patient: We report a 6-yr, 9-month-old boy born from a consanguineous relationship who presented shortly after birth with cyanosis, feeding difficulty, persistent jaundice, micropenis, and poor weight gain and growth rate. Laboratory data, including an undetectable TSH, low free T4, low IGF-I and IGF binding protein-3, prolactin deficiency, and LH and FSH deficiency were consistent with hypopituitarism. Arigid cervical spine leading to limited head rotation was noticed on follow-up examination. Magnetic resonance imaging revealed an apparently structurally normal cervical spine and a postcontrast hypointense lesion in the anterior pituitary. Results: Analysis of theLHX3gene revealed homozygosity for a novel single-base-pair deletion in exon 2. This mutation leads to a frame shift predicted to result in the production of short, inactive LHX3 proteins. The results of in vitro translation experiments are consistent with this prediction. The parents of the patients are heterozygotes, indicating a recessive mode of action for the deletion allele. Conclusions: The presence of a hypointense pituitary lesion and other clinical findings broadens the phenotype associated with LHX3 gene mutation.

UR - http://www.scopus.com/inward/record.url?scp=33644823897&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644823897&partnerID=8YFLogxK

U2 - 10.1210/jc.2005-2360

DO - 10.1210/jc.2005-2360

M3 - Article

C2 - 16394081

AN - SCOPUS:33644823897

VL - 91

SP - 747

EP - 753

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -