title: A novel RMRP mutation in a Spanish patient with cartilage-hair hypoplasia.
abstract: Cartilage-hair hypoplasia (CHH), or McKusick type metaphyseal chondrodysplasia, was first recognized as a distinct entity in the Old Order Amish in the USA, but was later identified in other groups, and found to be unusually frequent among Finns. CHH is highly pleiotropic with manifestations that include short stature, defective cellular immunity and predisposition to several cancers. CHH is caused by mutations in the RNA component of RNase MRP (RMRP, ribonuclease mitochondrial RNA processing) and is transmitted as an autosomal recessive trait. In the present work, a Spanish CHH patient was extensively characterized at the immunological and molecular DNA level. Several parameters of cellular and humoral immunity were analyzed in this patient: lymphocyte subpopulation, proliferative responsiveness in mitogen stimulation and quantification of serum immunoglobulins. Sequencing of the RMRP gene allowed identification of two mutations in the patient: a +4 C>T substitution previously described on one allele, and a duplication of 15 nucleotides at position -11 on the other allele. This mutation has not previously been described.
authors.affiliation: Department of Immunology, Hospital Universitario 12 de Octubre, Carretera de Andalucía s/n, 28041 Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Muñoz-Robles
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Allende
authors.forename: Julian
authors.initials: J
authors.lastname: Clemente
authors.forename: Sara
authors.initials: S
authors.lastname: Calleja
authors.forename: Pilar
authors.initials: P
authors.lastname: Varela
authors.forename: Luis
authors.initials: L
authors.lastname: Gonzalez
authors.forename: Paloma
authors.initials: P
authors.lastname: de Pablos
authors.forename: Estela
authors.initials: E
authors.lastname: Paz
authors.forename: Pablo
authors.initials: P
authors.lastname: Morales
mesh_terms: D001483:Base Sequence; D002356:Cartilage / Q000002:abnormalities*; D004252:DNA Mutational Analysis; D004722:Endoribonucleases / Q000235:genetics*; D005260:Female; D006197:Hair / Q000002:abnormalities*; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D013030:Spain
chemical_list: D004722:Endoribonucleases; C058330:mitochondrial RNA-processing endoribonuclease