ABSTRACT
Objective To understand the type and frequency of the gene mutation in exon 6 of phenylalanine hydroxylase(PAH) in the children of Ningxia,in order to provide foundation for phenylketonuria(PKU) gene diagnosis and prenatal diagnosis.Methods The exon 6 and flanking introns of 73 cases of classic PKU patients in Ningxia[all confirmed at Ningxia Neonatal Screening Center from Jan.2010 to Jun.2013,and distributed in Ningxia 22 County (city,district),aged from 15 days to 13 years,including 38 male cases,35 female cases,and Hui 39 cases,Han 34 cases] as well as 100 healthy newborn babies(Hui 50 cases;Han 50 cases) were sequentially analyzed by using the approach of PCR direct sequencing.Results There were 6 kinds of mutations detected,including EX6-96A ＞ G(6.85％),Q232X(2.74％),D222G(1.37％),V2301 (1.37％),R176X (0.68％) and N223I (0.68％).Mutation detection rate of exon 6 was 13.70％,and there were 3 mutation types:50.0％ missense mutation (3 types) ;33.3 ％ nonsense mutation (2 types) ;16.7％ cleavage site mutation(1 type).After reviewing the previous studies,the researchers had found out that EX6-96A ＞ G,Q232X and R176X were ever reported in China,and V2301 and D222G had been reported in our country for the first time but N223I was a new kind of PAH gene mutations were not been reported in the world.Conclusions It has defined the gene type and frequency of PAH gene mutations in exon 6 in the children of Ningxia and it will enrich the research of PKU in this area,and provide the basis for the development of gene diagnosis of PKU.
ABSTRACT
Introducción: La esclerosis tuberosa (ET) es una anomalía del desarrollo genéticamente determinada, susceptible de originar tumores y / o hamartomas del sistema nervioso; formación de angiofibromas en piel y afectación en otros órganos. Objetivos: Describir las características clínicas de los pacientes pediátricos con diagnóstico de ET controlados en el Servicio de Neurología Pediátrica del Instituto Autónomo Hospital Universitario de los Andes. Pacientes y métodos: Se realizó un estudio observaciones, de tipo serie de casos desde enero 2005 hasta enero de 2010. Introducción: Se reportaron 9 casos que cumplieron los criterios diagnósticos de Et, entre 2 a 12 años, con una distribución en cuanto a sexo, 56% varones y 44% mujeres siendo la edad preescolar el grupo erario predominante. Solo 11% de los pacientes presentó algún familiar con ET, lo que representó una alta frecuencia de mutaciones nuevas. Discusión : El signo clínico más temprano y frecuente encontrado fueron las manchas hipocrómicas en hoja de fresno, con un porcentaje significativo de rasgos autistas 44% versus 9% de los niños según lo reportado en la literatura. No es posible establecer la asociación entre el número de tuberosas corticales y la existencia temprana de convulsiones o retardo mental. Conclusiones: La existencia de esta entidad en nuestro medio presenta características similares a las descritas en la experiencia internacional. Es imprescindible el manejo por parte de un equipo multidisciplinario. A pesar de que la ET es una entidad con patrón de herencia autosómico dominante, la presente serie de casos demuestra una gran frecuencia de mutaciones nuevas.
Introduction: Tuberous sclerosis (TS) is a developmental anomaly genetically determined, susceptible to cause tumors and / or hamartomas of the nervous system, formation of angiofibromas in skin, and affectation of others organs. Objetives: To describe clinical characteristics of pediatric patients with TS evaluated in the Child Neurology Service of the Institute Autonomous University Los Andes. Patients and methods: We realized an observational study of type case series from january 2005 to january 2010. Results: Were reported 9 cases that presented diagnostic criteria of TS, between 2-12 years, with a distribution similar in sex, 56% male and 44 females being the age predominant age group preschool. Only 11% patients had a family member with TS, which represent a high frequency of new mutations. Discussion: The earliest clinical sign and frequent is hypo chromic stains were found in "ash leaf" with a significant percentage of autistic features 44% versus 9% of children reported to the literature. It is not possible to establish the association between the number of cortical tubers and early existence of seizures or mental retardation. Conclusion: The existence of this early in our environment has similar characteristics to those described in international experience. It is essential to management by a multidisciplinary group. Although TS is an entity with autosomal dominos inheritance pattern, this series of cases shows a high frequency of new mutations.