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.

Low prevalence of p.G352fsdelG mutation in phenylketonuria patients from Morocco.

OBJECTIVE: Frameshift mutation p.G352fsdelG in the PAH gene was recently reported as the most common mutation in Moroccan patients with phenylketonuria (PKU). This result, if confirmed, would considerably facilitate genetic counseling and molecular diagnosis of the disease in Morocco. Given that the incidence of PKU in the Mediterranean region is estimated at between 1/4000 and 1/10,000, this mutation would be harbored by many Moroccans. We aimed to estimate the frequency of heterozygotes for the p.G352fsdelG mutation in Moroccan newborns. MATERIALS AND METHODS: In this study, we used a reliable TaqMan(®) real-time polymerase chain reaction to detect the mutation p.G352fsdelG in the PAH gene in 250 unrelated Moroccan newborns. DNA was extracted from umbilical cord blood with maternal consent. RESULTS: The supposed recurrent mutation p.G352fsdelG was found in none of the 250 tested newborns. Therefore, the frequency of heterozygotes for this mutation would be less than 1/250, and the incidence of patients with PKU homozygous for this mutation would not exceed 1/100,000. CONCLUSION: The p.G352fsdelG mutation in the PAH gene does not appear to be prevalent in the Moroccan population and would be responsible for only few cases of PKU. The previous report of this anomaly as being responsible for 62.5% of PKU patients in Morocco could be explained by selection bias.