The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform
Amrit Bhangoo - One of the best experts on this subject based on the ideXlab platform.
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LHX3 deficiency presenting in the United States with severe developmental delay in a child of Syrian refugee parents.
Endocrinology diabetes & metabolism case reports, 2018Co-Authors: Susan Ahern, Mark Daniels, Amrit BhangooAbstract:In this case report, we present a novel mutation in Lim-homeodomain (LIM-HD) Transcription Factor, LHX3, manifesting as combined pituitary hormone deficiency (CPHD). This female patient was originally diagnosed in Egypt during infancy with Diamond Blackfan Anemia (DBA) requiring several blood transfusions. Around 10 months of age, she was diagnosed and treated for central hypothyroidism. It was not until she came to the United States around two-and-a-half years of age that she was diagnosed and treated for growth hormone deficiency. Her response to growth hormone replacement on linear growth and muscle tone were impressive. She still suffers from severe global development delay likely due to delay in treatment of congenital central hypothyroidism followed by poor access to reliable thyroid medications. Her diagnosis of DBA was not confirmed after genetic testing in the United States and her hemoglobin normalized with hormone replacement therapies. We will review the patient's clinical course as well as a review of LHX3 mutations and the associated phenotype. Learning points: Describe an unusual presentation of undertreated pituitary hormone deficiencies in early life Combined pituitary hormone deficiency due to a novel mutation in pituitary Transcription Factor, LHX3 Describe the clinical phenotype of combined pituitary hormone deficiency due to LHX3 mutations.
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LHX3 deficiency presenting in the United States with severe developmental delay in a child of Syrian refugee parents
Bioscientifica, 2018Co-Authors: Amrit BhangooAbstract:In this case report, we present a novel mutation in Lim-homeodomain (LIM-HD) Transcription Factor, LHX3, manifesting as combined pituitary hormone deficiency (CPHD). This female patient was originally diagnosed in Egypt during infancy with Diamond Blackfan Anemia (DBA) requiring several blood transfusions. Around 10 months of age, she was diagnosed and treated for central hypothyroidism. It was not until she came to the United States around two-and-a-half years of age that she was diagnosed and treated for growth hormone deficiency. Her response to growth hormone replacement on linear growth and muscle tone were impressive. She still suffers from severe global development delay likely due to delay in treatment of congenital central hypothyroidism followed by poor access to reliable thyroid medications. Her diagnosis of DBA was not confirmed after genetic testing in the United States and her hemoglobin normalized with hormone replacement therapies. We will review the patient’s clinical course as well as a review of LHX3 mutations and the associated phenotype
Serge Amselem - One of the best experts on this subject based on the ideXlab platform.
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Symptomatic Heterozygotes and Prenatal Diagnoses in a Nonconsanguineous Family with Syndromic Combined Pituitary Hormone Deficiency Resulting from Two Novel LHX3 Mutations
The Journal of clinical endocrinology and metabolism, 2012Co-Authors: Marie-laure Sobrier, Cécile Brachet, Marie-pierre Vie-luton, Christelle Perez, Bruno Copin, Marie Legendre, Claudine Heinrichs, Serge AmselemAbstract:Context: Only 11 mutations have been reported in the Transcription Factor LHX3, known to be important for the development of the pituitary and motor neurons. All patients were homozygous, with various syndromic forms of combined pituitary hormone deficiency (CPHD), hampering to allocate, in these consanguineous patients, the respective contribution of LHX3 and additional genes to each symptom. Objective: The aim of the study was to report the family history and the molecular basis of a nonconsanguineous patient with syndromic CPHD. Patient: The patient, who presented at birth with respiratory distress, had a syndromic CPHD, including severe scoliosis, and normal intelligence. His father and paternal grandmother displayed limited head rotation. Results: Two new LHX3 defects were identified. The paternally inherited c.252-3C>G mutation, which disrupts an acceptor splice site, would lead to severely truncated proteins containing a single LIM domain, resembling LIM-only proteins. Coexpression studies revealed...
Sally A Camper - One of the best experts on this subject based on the ideXlab platform.
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Mechanisms underlying pituitary hypoplasia and failed cell specification in LHX3-deficient mice.
Developmental Biology, 2007Co-Authors: Buffy S. Ellsworth, Darcy L. Butts, Sally A CamperAbstract:The LIM-homeodomain Transcription Factor, LHX3, is essential for pituitary development in mouse and man. LHX3 engineered null mice have profound pituitary hypoplasia that we find is attributable to an increase in cell death early in pituitary development. Dying cells are localized to regions of TPIT expression indicating that cell death may contribute to the severe reduction in differentiated corticotrope cells and lower expression of the corticotrope Transcription Factors, TPIT and NEUROD1. LHX3 deficiency also results in dorsal ectopic expression of Transcription Factors characteristic of gonadotropes, SF1 and ISL1, but no gonadotropin expression. This apparent disturbance of cell differentiation may be due, in part, to loss of NOTCH2. NOTCH2 is normally expressed in the pituitary at the boundary between dorsal, proliferating cells and ventral, differentiating cells and is important for maintaining dorsal-ventral patterning in other organs. Thus, LHX3 contributes significantly to pituitary development by maintaining normal dorsal-ventral patterning, cell survival, and normal expression of corticotrope-specific Transcription Factors, which are necessary for repressing ectopic gonadotrope differentiation.
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PITX Genes Are Required for Cell Survival and LHX3 Activation
Molecular endocrinology (Baltimore Md.), 2005Co-Authors: Michael A. Charles, Sally A Camper, Hoonkyo Suh, Tord A. Hjalt, Jacques Drouin, Philip J. GageAbstract:The PITX family of Transcription Factors regulate the development of many organs. Pitx1 mutants have a mild pituitary phenotype, but Pitx2 is necessary for the development of Rathke's pouch, expression of essential Transcription Factors in gonadotropes, and expansion of the Pit1 lineage. We report that lack of Pitx2 causes the pouch to undergo excessive cell death, resulting in severe pituitary hypoplasia. Transgenic overexpression of PITX2 in the pituitary can increase the gonadotrope population, suggesting that the absolute concentration of PITX2 is important for normal pituitary cell lineage expansion. We show that PITX1 and PITX2 proteins are present in similar expression patterns throughout pituitary development and in the mature pituitary. Both Transcription Factors are preferentially expressed in adult gonadotropes and thyrotropes, suggesting the possibility of overlap in maintenance of adult pituitary functions within these cell types. Double knockouts of Pitx1 and Pitx2 exhibit severe pituitary hypoplasia and fail to express the Transcription Factor LHX3. This indicates that these PITX genes are upstream of LHX3 and have compensatory roles during development. Thus, the combined dosage of these PITX family members is vital for pituitary development, and their persistent coexpression in the adult pituitary suggests a continued role in maintenance of pituitary function.
Annette Grueters - One of the best experts on this subject based on the ideXlab platform.
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Novel mutations in LHX3 are associated with hypopituitarism and sensorineural hearing loss
Human molecular genetics, 2008Co-Authors: Anna Rajab, Daniel Kelberman, Sandra C. P. De Castro, Heike Biebermann, Hala Shaikh, Kerra Pearce, Catherine M. Hall, Guftar Shaikh, Dianne Gerrelli, Annette GruetersAbstract:Homozygous loss-of-function mutations in the Transcription Factor LHX3 have been associated with hypopituitarism with structural anterior pituitary defects and cervical abnormalities with or without restricted neck rotation. We report two novel recessive mutations in LHX3 in four patients from two unrelated pedigrees. Clinical evaluation revealed that all four patients exhibit varying degrees of bilateral sensorineural hearing loss, which has not been previously reported in association with LHX3 mutations, in addition to hypopituitarism including adrenocorticotropic hormone deficiency and an unusual skin and skeletal phenotype in one family. Furthermore, re-evaluation of three patients previously described with LHX3 mutations showed they also exhibit varying degrees of bilateral sensorineural hearing loss. We have investigated a possible role for LHX3 in inner ear development in humans using in situ hybridization of human embryonic and fetal tissue. LHX3 is expressed in defined regions of the sensory epithelium of the developing inner ear in a pattern overlapping that of SOX2, which precedes the onset of LHX3 expression and is known to be required for inner ear and pituitary development in both mice and humans. Moreover, we show that SOX2 is capable of binding to and activating Transcription of the LHX3 proximal promoter in vitro. This study therefore extends the phenotypic spectrum associated with LHX3 mutations to encompass variable sensorineural hearing loss and suggests a possible interaction between LHX3 and SOX2 likely to be important for development of both the inner ear and the anterior pituitary in human embryonic development.
Marie-laure Sobrier - One of the best experts on this subject based on the ideXlab platform.
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Symptomatic Heterozygotes and Prenatal Diagnoses in a Nonconsanguineous Family with Syndromic Combined Pituitary Hormone Deficiency Resulting from Two Novel LHX3 Mutations
The Journal of clinical endocrinology and metabolism, 2012Co-Authors: Marie-laure Sobrier, Cécile Brachet, Marie-pierre Vie-luton, Christelle Perez, Bruno Copin, Marie Legendre, Claudine Heinrichs, Serge AmselemAbstract:Context: Only 11 mutations have been reported in the Transcription Factor LHX3, known to be important for the development of the pituitary and motor neurons. All patients were homozygous, with various syndromic forms of combined pituitary hormone deficiency (CPHD), hampering to allocate, in these consanguineous patients, the respective contribution of LHX3 and additional genes to each symptom. Objective: The aim of the study was to report the family history and the molecular basis of a nonconsanguineous patient with syndromic CPHD. Patient: The patient, who presented at birth with respiratory distress, had a syndromic CPHD, including severe scoliosis, and normal intelligence. His father and paternal grandmother displayed limited head rotation. Results: Two new LHX3 defects were identified. The paternally inherited c.252-3C>G mutation, which disrupts an acceptor splice site, would lead to severely truncated proteins containing a single LIM domain, resembling LIM-only proteins. Coexpression studies revealed...