Clinical case seminar: a novel LHX3 mutation presenting as combined pituitary hormonal deficiency.
BACKGROUND
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.


METHODS
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. A rigid 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 the LHX3 gene 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.
Bhangoo
Amrit P S
AP
Pediatric Endocrinology Division, Infant's and Children's Hospital of Brooklyn at Maimonides, Brooklyn, New York 11219, USA.
Hunter
Chad S
CS
Savage
Jesse J
JJ
Anhalt
Henry
H
Pavlakis
Steven
S
Walvoord
Emily C
EC
Ten
Svetlana
S
Rhodes
Simon J
SJ
D000595:Amino Acid Sequence; D002648:Child; D003241:Consanguinity; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010902:Pituitary Gland / Q000473:pathology; D010907:Pituitary Hormones / Q000172:deficiency*; D017384:Sequence Deletion; D014157:Transcription Factors
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; D010907:Pituitary Hormones; D014157:Transcription Factors