RMRP gene sequence analysis confirms a cartilage-hair hypoplasia variant with only skeletal manifestations and reveals a high density of single-nucleotide polymorphisms

Détails

ID Serval
serval:BIB_FC05916E6145
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Institution
Titre
RMRP gene sequence analysis confirms a cartilage-hair hypoplasia variant with only skeletal manifestations and reveals a high density of single-nucleotide polymorphisms
Périodique
Clinical Genetics
Auteur(s)
Bonafe  L., Schmitt  K., Eich  G., Giedion  A., Superti-Furga  A.
ISSN
0009-9163
Statut éditorial
Publié
Date de publication
02/2002
Peer-reviewed
Oui
Volume
61
Numéro
2
Pages
146-51
Notes
Case Reports
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb
Résumé
Mutations in the RMRP gene that codes for an RNA subunit of the MRP RNAse complex are the cause of cartilage-hair hypoplasia (CHH; MIM 250250). We tested the hypothesis that recessive metaphyseal dysplasia without hypotrichosis (M1M 250460), a disorder presenting with short stature and metaphyseal dysplasia similar to CHH, but lacking hair anomalies, immunodeficiency and other extra skeletal features, might be allelic to CHH. We identified four mutation-carrying alleles segregating with the skeletal phenotype in two unrelated boys and their parents. One allele carried the common Finnish mutation +70A--> G; the remaining three carried +195C--> T, +238C--> T, and dupAAGCTGAGGACG at -2. Sequencing 120 alleles from a control group revealed an unusually high density of single-nucleotide polymorphisms in and around the RMRP gene: the biological significance of this finding is unclear. We conclude that recessive metaphyseal dysplasia without hypotrichosis is a variant of CHH, manifesting only as short stature and metaphyseal dysplasia. Precise diagnosis of this form of metaphyseal dysplasia is not without importance because of recessive inheritance with corresponding recurrence risk, as well as because of potential complications such as anaemia, susceptibility to infections and the increased likelihood of developing cancer. The short stature and metaphyseal changes associated with cone-shaped epiphyses of the hands should raise the diagnostic possibility of a CHH-related disorder that can then be confirmed by mutation analysis.
Mots-clé
Alleles Base Sequence Bone and Bones/*abnormalities Cartilage/*abnormalities Child DNA Mutational Analysis Hair Humans Male Molecular Sequence Data *Mutation Phenotype *Polymorphism, Single Nucleotide Ribonucleases/*genetics
Pubmed
Web of science
Création de la notice
21/01/2008 12:50
Dernière modification de la notice
20/08/2019 16:27
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