Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia

Citation
M. Ridanpaa et al., Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia, CELL, 104(2), 2001, pp. 195-203
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL
ISSN journal
0092-8674 → ACNP
Volume
104
Issue
2
Year of publication
2001
Pages
195 - 203
Database
ISI
SICI code
0092-8674(20010126)104:2<195:MITRCO>2.0.ZU;2-X
Abstract
The recessively inherited developmental disorder, cartilage-hair hypoplasia (CHH) is highly pleiotropic with manifestations including short stature, d efective cellular immunity, and predisposition to several cancers. The endo ribonuclease RNase MRP consists of an RNA molecule bound to several protein s. It has at least two functions, namely, cleavage of RNA in mitochondrial DNA synthesis and nucleolar cleaving of pre-rRNA. We describe numerous muta tions in the untranslated RMRP gene that cosegragate with the CHH phenotype . Insertion mutations immediately upstream of the coding sequence silence t ranscription while mutations in the transcribed region do not. The associat ion of protein subunits with RNA appears unaltered. We conclude that mutati ons in RMRP cause CHH by disrupting a function of RNase MRP RNA that affect s multiple organ systems.