[Diagnosis of genetic mental retardation. Protocol of study]

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.

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.

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.