Publication
Title
Mutation of **TBCE** causes hypoparathyroidism- retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome
Author
Abstract
The syndrome of congenital hypoparathyroidism, mental retardation, facial dysmorphism and extreme growth failure (HRD or SanjadSakati syndrome; OMIM 241410) is an autosomal recessive disorder reported almost exclusively in Middle Eastern populations1, 2, 3. A similar syndrome with the additional features of osteosclerosis and recurrent bacterial infections has been classified as autosomal recessive KennyCaffey syndrome4 (AR-KCS; OMIM 244460). Both traits have previously been mapped to chromosome 1q4344 (refs 5,6) and, despite the observed clinical variability, share an ancestral haplotype, suggesting a common founder mutation7. We describe refinement of the critical region to an interval of roughly 230 kb and identification of deletion and truncation mutations of TBCE in affected individuals. The gene TBCE encodes one of several chaperone proteins required for the proper folding of alpha-tubulin subunits and the formation of alphabeta-tubulin heterodimers. Analysis of diseased fibroblasts and lymphoblastoid cells showed lower microtubule density at the microtubule-organizing center (MTOC) and perturbed microtubule polarity in diseased cells. Immunofluorescence and ultrastructural studies showed disturbances in subcellular organelles that require microtubules for membrane trafficking, such as the Golgi and late endosomal compartments. These findings demonstrate that HRD and AR-KCS are chaperone diseases caused by a genetic defect in the tubulin assembly pathway, and establish a potential connection between tubulin physiology and the development of the parathyroid.
Language
English
Source (journal)
Nature genetics. - New York, N.Y.
Publication
New York, N.Y. : 2002
ISSN
1061-4036
Volume/pages
32:3(2002), p. 448-452
ISI
000179034800025
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 05.06.2012
Last edited 06.08.2017