L Rodríguez-Revenga Bodi

PubMed2006

[Genetic mental retardation].

INTRODUCTION: Mental retardation is a frequently occurring disorder with a major impact on the life of the affected person, the family and society, with an estimated incidence of 1-3% in developed countries. Among the etiologies that cause mental retardation it would appear that 30% have a genetic origin, 15% have an environmental origin, and the rest have an unknown origin. AIM. To report the genetic causes of mental retardation and the new molecular techniques used in order to reach a diagnosis. The identification of the causes of mental retardation is of great interest due to the consequences it has in the intervention, prognosis, estimation of risk of recurrence and its prevention. DEVELOPMENT: Causes of mental retardation are extremely heterogeneous. Genetic causes can be classified as chromosomal alterations (aneuploidies, subtelomeric rearrangements, microdeletion or microduplication syndrome), monogenic, metabolic, or multifactorial alterations. Thanks to the development of high-resolution new techniques -comparative genomic hybridization (CGH) arrays, and multiplex ligation probe amplification (MLPA)- now we are able to detect microdeletions and microduplication all over the genome, which might be related with mental retardation. CONCLUSIONS: The genetic causes of mental retardation are highly heterogeneous and complex. Nowadays and thanks to the new molecular techniques we are able to perform several studies, even though almost half of cases remain undiagnosed. In those undiagnosed cases with positive familial history a genetic counseling can be provided. However, in order to perform a prenatal or a preimplantational study a genetic diagnosis is required.

Chromosome Mapping↗

PubMed2006

[Diagnosis of genetic mental retardation. Protocol of study].

INTRODUCTION: The study of mental retardation (MR) is one of the most complex fields in human genetics, due to the fact that it presents a very high degree of clinical and genetic heterogeneity, and both the genetic bases and the environmental factors that act upon them are extremely complex. At the present time almost half of the cases of MR remain undiagnosed. AIM. To present a protocol for laboratory work using the technology that is currently available to reach a diagnosis of MR. DEVELOPMENT: The first step is to evaluate the patient with a thorough clinical examination and by obtaining information about the personal and family history. A suspected diagnosis of one or several syndromes that involve MR must be confirmed, if possible, in the laboratory with the appropriate technique. In cases of MR with no clinical suspicion of any specific syndrome, three tests must be conducted: karyotype, molecular study of the expansion of CGG in the FMR1 gene, and study of the subtelomeric regions. If the study is negative and we are dealing with a familial case with a suitable structure, a linkage study must be performed. As far as sporadic cases are concerned, it is difficult to advance in a routine manner although some tests allow screening several genes determinations to be carried out on several genes at the same time. Other techniques permit to investigate in greater depth, such as screening for genes responsible for non-specific X-linked MR or CGH-arrays (arrays based on compared genomic hybridisation) for the whole genome or for a particular chromosome. At the present time, however, such techniques are limited to research projects or very special cases. CONCLUSIONS: We propose a study protocol and highlight the importance of its use to obtain maximum performance in order to reach a diagnosis that allows us to give genetic counselling and offer a prenatal diagnosis for future generations.

Child↗