Document Detail


Mutation in the TBCE gene is associated with hypoparathyroidism-retardation-dysmorphism syndrome featuring pituitary hormone deficiencies and hypoplasia of the anterior pituitary and the corpus callosum.
MedLine Citation:
PMID:  19491227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Hypoparathyroidism-retardation-dysmorphism (HRD) syndrome, an autosomal recessive disorder characterized by distinct clinical, biochemical, and genetic abnormalities, is characterized by severe short stature, the etiology of which is unclear. Homozygous mutation of the tubulin cofactor E (TBCE) gene leading to loss of four amino acids (c.155-166del12; p.del 52-55) in the TBCE protein has been associated with the syndrome. AIM: The aim of the study was to describe the clinical, biochemical, and neuroradiological features of children with genetically proven HRD syndrome. METHODS: Six children from four independent Middle Eastern pedigrees with clinical features of HRD syndrome were confirmed to have the previously reported homozygous mutation in TBCE (c.155-166del12) and were investigated with magnetic resonance imaging (MRI) of the brain and standard pituitary function testing. RESULTS: Cranial MRI in all children showed severe hypoplasia of the anterior pituitary and corpus callosum, with decreased white matter bulk. Four of five children tested had subnormal GH and cortisol responses to glucagon, and plasma IGF-I concentration was low in all six children. Cortisol response to synacthen was suboptimal in one of three patients tested. Male children (n = 3) had clinical features suggestive of hypogonadotropic hypogonadism. CONCLUSION: GH insufficiency, hypocortisolemia, and abnormal cranial MRI appear to be associated with HRD syndrome and may contribute in part to the short stature. Our data support the need for longer term monitoring for evolving pituitary hormone deficiencies and raise the possibility that TBCE may play a role in development of the anterior pituitary, corpus callosum, and white matter in addition to the parathyroid glands.
Authors:
Raja Padidela; Dan Kelberman; Martin Press; M Al-Khawari; Peter C Hindmarsh; Mehul T Dattani
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Publication Detail:
Type:  Case Reports; Journal Article     Date:  2009-06-02
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  94     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-06     Completed Date:  2009-08-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2686-91     Citation Subset:  AIM; IM    
Affiliation:
Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College of London, Great Ormond Street Hospital for Children, 30 Guilford Street, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Multiple / genetics*
Child, Preschool
Corpus Callosum / pathology*
Female
Human Growth Hormone / deficiency*
Humans
Hypoparathyroidism / genetics*
Infant
Magnetic Resonance Imaging
Male
Mental Retardation
Molecular Chaperones / genetics*
Mutation*
Pituitary Gland, Anterior / pathology*
Syndrome
Chemical
Reg. No./Substance:
0/Molecular Chaperones; 0/TBCE protein, human; 12629-01-5/Human Growth Hormone

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