Abstract
Intellectual disability (ID) has been defined as a significant limitation in both intellectual functioning (IQ<70) and concurrent limitations in conceptual, social and practical adaptive skills, manifesting before the age of 18. The details about known genetic aetiologies associated with ID are discussed in chapter 1. Indonesia ranks fourth on the list of countries with the largest population in the world, indicating that also the ID population must be large. However, only a partial genetic diagnostic work-up of the ID population in Indonesia has been performed. This study aimed at recording an aetiological diagnosis of ID as well as trying to determine the prevalence of cytogenetic and some molecular diagnoses, performing phenotype-genotype correlation studies, and defining a diagnostic protocol for ID which is applicable in the Indonesian context. In chapter 2 we determined the frequency of cytogenetic abnormalities in a cohort of Indonesian individuals with ID using conventional cytogenetic analysis confirmed by some stand-alone molecular tests. In chapter 3 we determined the frequency of Fragile X syndrome (FXS) in males and females, and documented their relatives with a similar disorder. In chapter 4 we determined the frequency of subtelomeric deletions and duplications using MLPA in a cohort of Indonesian individuals with ID who had a normal karyotype and who were FXS negative. In chapter 5 we investigated a subset of ID individuals suspected of having a specific syndrome. A case with Mowat-Wilson syndrome and the results of sequencing of several genes involved in autosomal recessive primary microcephaly are described. In chapter 6, the implication of this work including the establishment of a diagnostic protocol for the Indonesian setting is described. In addition, a general discussion and future directions towards a better genetic diagnostic workup in Indonesia having limited laboratory facilities are also provided.
