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Submitted on October 27, 2005
Accepted on December 27, 2005
Pediatric Endocrinology Division of Infant's and Children's Hospital of Brooklyn at Maimonides, Brooklyn, NY.; Department of Biology, Indiana University-Purdue University, Indianapolis, IN.; Pediatric Endocrinology Division of Saint Barnabas Medical Center, Livingston, NJ.; Pediatric Neurology Division of Infant's and Children's Hospital of Brooklyn at Maimonides, Brooklyn, NY.; Department of Pediatrics, Section of Endocrinology and Diabetology, Indiana University School of Medicine, Indianapolis, IN.; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN
* To whom correspondence should be addressed. E-mail: tenlana{at}aol.com.
Context: LHX3 encodes LIM homeodomain class transcription factors with important roles in pituitary and nervous system development. The only prior 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, poor weight gain and growth rate. Laboratory data, including an undetectable thyroid-stimulating hormone, low free thyroxine, low IGF-I and IGFBP-3, prolactin deficiency, LH and follicle-stimulating hormone 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 post-contrast hypointense lesion in the anterior pituitary.
Results: Analysis of the LHX3 gene revealed homozygosity for a novel single bp deletion in exon 2. This mutation leads to a frame shift predicted to result in the product of short, inactive LHX3 proteins. The results of in vitro translation experiments are consistent with this prediction. The parents of the patients are heterozygous, 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.
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