X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

Apparent higher frequency of phenylketonuria in the Mexican state of Jalisco

The geographic origin of Mexican patients with phenylketonuria (PKU) in Mexico City and in southern California was studied. Compared to patients with other metabolic disorders, patients with PKU were significantly more likely to have originated from the Los Altos region of the state of Jalisco and its environs. The incidence of PKU among mentally retarded students attending special education schools was found to be significantly higher in Jalisco (particularly the Los Altos region) than in the neighboring state of Guanajuato (1.09% vs 0.3%). These results strongly suggest a 'population of origin' effect, the mutant allele(s) having been introduced by the Spanish ancestors of the current population. Our findings also support the addition of PKU to the neonatal screening program for this region of Mexico

Apparent higher frequency of phenylketonuria in the Mexican state of Jalisco

The geographic origin of Mexican patients with phenylketonuria (PKU) in Mexico City and in southern California was studied. Compared to patients with other metabolic disorders, patients with PKU were significantly more likely to have originated from the Los Altos region of the state of Jalisco and its environs. The incidence of PKU among mentally retarded students attending special education schools was found to be significantly higher in Jalisco (particularly the Los Altos region) than in the neighboring state of Guanajuato (1.09% vs 0.3%). These results strongly suggest a 'population of origin' effect, the mutant allele(s) having been introduced by the Spanish ancestors of the current population. Our findings also support the addition of PKU to the neonatal screening program for this region of Mexico