Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47)

Department of Medical Genetics, University of Tübingen, Tübingen, Germany.
Neurogenetics (Impact Factor: 2.88). 01/2012; 13(1):73-6. DOI: 10.1007/s10048-012-0314-0
Source: PubMed


We recently identified a new locus for spastic paraplegia type 47 (SPG47) in a consanguineous Arabic family with two affected siblings with progressive spastic paraparesis,intellectual disability, seizures, periventricular white matter changes and thin corpus callosum. Using exome sequencing, we now identified a novel AP4B1 frameshift mutation (c.664delC) in this family. This mutation was homozygous in both affected siblings and heterozygous in both parents. The mutant allele was absent in 316 Caucasian and 200 ethnically matched control chromosomes. We propose that AP4B1 mutations cause SPG47 and should be considered in early onset spastic paraplegia with intellectual disability.

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    • "Previously, mutations in two subunits, AP4M1 and AP4E1, of the adaptor protein complex 4 (AP4) were found associated with AR spastic tetraplegia as well as cerebral palsy and microcephaly, respectively (Verkerk et al., 2009; Moreno-De-Luca et al., 2011). But recently, pathogenic mutations in three AP4 subunits, AP4S1, AP4B1, and AP4E1, have also been identified in consanguineous families presenting with early-onset complex SPG, severe ID, microcephaly, inability to walk, and epilepsy (Abou Jamra et al., 2011); AP4B1 pathogenic mutations are also responsible for SPG type 47 (Bauer et al., 2012). Since patients carrying AP4 mutations share many clinical features, the existence of a complex AP4-deficiency syndrome, characterized by severe ID, growth retardation, stereotypic laughter, progressive spasticity, cerebral palsy, and inability to walk, has been suggested, further supporting the key role of AP4-mediated trafficking in brain development and functioning (Abou Jamra et al., 2011). "
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