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Abstract

X-linked intellectual disability (XLID) is a heterogeneous disorder, and mutations in more than 90 genes have been associated with XLID to date. We report on a large multi-generational German family in which the affected male family members had nonsyndromic intellectual disability, that is, they had neither abnormal body measurements nor any other significant clinical problems. Molecular genetic analysis revealed a frameshift mutation in GDI1 (c.1185_1186delAG; Ser396ProfsX15) that co-segregated with the disease. GDI1 encodes for the GDP-dissociation inhibitor alpha (alphaGDI), a protein involved in the regulation of the activity of Rab GTPases. Only three families with GDI1 mutations have been reported so far. The present family supports the lack of additional phenotypic features in patients with GDI1 mutations, rendering a clinical diagnosis of GDI1-associated XLID impossible. Thus, this family not only broadens the spectrum of GDI1 mutations but also emphasizes the need for parallel testing of all known genes associated with ID in patients with an unspecific phenotype.