Document Detail


Mutation and gene copy number analyses of six pituitary transcription factor genes in 71 patients with combined pituitary hormone deficiency: identification of a single patient with LHX4 deletion.
MedLine Citation:
PMID:  20534763     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Mutations of multiple transcription factor genes involved in pituitary development have been identified in a minor portion of patients with combined pituitary hormone deficiency (CPHD). However, copy number aberrations involving such genes have been poorly investigated in patients with CPHD. OBJECTIVE: We aimed to report the results of mutation and gene copy number analyses in patients with CPHD. SUBJECTS AND METHODS: Seventy-one Japanese patients with CPHD were examined for mutations and gene copy number aberrations affecting POU1F1, PROP1, HESX1, LHX3, LHX4, and SOX3 by PCR-direct sequencing and multiplex ligation-dependent probe amplification. When a deletion was indicated, it was further studied by fluorescence in situ hybridization, oligoarray comparative genomic hybridization, and serial sequencing for long PCR products encompassing the deletion junction. RESULTS: We identified a de novo heterozygous 522,009-bp deletion involving LHX4 in a patient with CPHD (GH, TSH, PRL, LH, and FSH deficiencies), anterior pituitary hypoplasia, ectopic posterior pituitary, and underdeveloped sella turcica. We also identified five novel heterozygous missense substitutions (p.V201I and p.H387P in LHX4, p.T63M and p.A322T in LHX3, and p.V53L in SOX3) that were assessed as rare variants by sequencing analyses for control subjects and available parents and by functional studies and in silico analyses. CONCLUSIONS: The results imply the rarity of abnormalities affecting the six genes in patients with CPHD and the significance of the gene copy number analysis in such patients.
Authors:
Sumito Dateki; Maki Fukami; Ayumi Uematsu; Masayuki Kaji; Manami Iso; Makoto Ono; Michiyo Mizota; Susumu Yokoya; Katsuaki Motomura; Eiichi Kinoshita; Hiroyuki Moriuchi; Tsutomu Ogata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-09
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-05     Completed Date:  2010-08-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4043-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya, Tokyo 157-8535, Japan.
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MeSH Terms
Descriptor/Qualifier:
Female
Gene Deletion*
Homeodomain Proteins / genetics*
Humans
Hypopituitarism / genetics*
In Situ Hybridization, Fluorescence
Male
Polymerase Chain Reaction
Transcription Factors / genetics*
Chemical
Reg. No./Substance:
0/Homeodomain Proteins; 0/LHX4 protein, human; 0/Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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