title: Novel GDI1 mutation in a large family with nonsyndromic X-linked intellectual disability.
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 (αGDI), 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.
authors: Humangenetik Ulm MVZ, Ulm, Germany.
authors: Gertrud
authors: G
authors: Strobl-Wildemann
authors: Vera M
authors: VM
authors: Kalscheuer
authors: Hao
authors: H
authors: Hu
authors: Klaus
authors: K
authors: Wrogemann
authors: Hans-Hilger
authors: HH
authors: Ropers
authors: Andreas
authors: A
authors: Tzschach
mesh_terms: D002648:Child; D002675:Child, Preschool; D005091:Exons; D019066:Facies; D005260:Female; D016368:Frameshift Mutation; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype
chemical_list: C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors