Novel Mutation and Structural RNA Analysis of the Noncoding RNase MRP Gene in Cartilage-Hair Hypoplasia.
Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder which is characterized by bone metaphysis anomalies with manifestations that include short stature, defective cellular immunity, and predisposition to several cancers. It is caused by mutations in RMRP, which is transcribed as an RNA component of the mitochondrial RNA-processing ribonuclease. We report the clinical and molecular data of a Moroccan patient with CHH. Sequencing of RMRP identified 2 mutations in the patient: the known mutation g.97G>A and the variation g.27G>C, which has not been reported previously. Given the high mutational heterogeneity, the high frequency of variations in the region, and the fact that RMRP is a non-coding gene, assigning the pathogenicity to RMRP mutations remains a difficult task. Therefore, we compared the characteristics of the primary and secondary structures of mutated RMRP sequences. The location of our mutations within the secondary structure of the RMRP molecule revealed that the novel g.27G>C mutation causes a disruption in the Watson-Crick base pairing, which results in an impairment of a highly conserved P3 domain. Our work prompts considering the consequences of novel RMRP nucleotide variations on conserved RNA structures to gain insights into the pathogenicity of mutations.
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V, France ; Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco, France.
Imane
I
Cherkaoui Jaouad
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V, France ; Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco, France.
Fatima Z
FZ
Laarabi
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V, France ; Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco, France.
Siham
S
Chafai Elalaoui
INSERM UMR-781, Hôpital Necker-Enfants Malades, Université Paris Descartes, France ; Département de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Paris, France.
Stanislas
S
Lyonnet
Département de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Paris, France.
Alexandra
A
Henrion-Caude
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V, France ; Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco, France.
Abdelaziz
A
Sefiani
Cartilage-hair hypoplasia; Mutational analysis; RNA folding ; RNase P/MRP