Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47)
- First Online:
- 503 Downloads
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.
KeywordsSPG47 AP4 AP4B1 Spastic paraplegia Complicated
- 7.Abou Jamra R, Philippe O, Raas-Rothschild A, Eck SH, Graf E, Buchert R, Borck G, Ekici A, Brockschmidt FF, Nöthen MM, Munnich A, Strom TM, Reis A, Colleaux L (2011) Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. Am J Hum Genet 88:788–795PubMedCrossRefGoogle Scholar
- 8.Moreno-De-Luca A, Helmers SL, Mao H, Burns TG, Melton AM, Schmidt KR, Fernhoff PM, Ledbetter DH, Martin CL (2011) Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability. J Med Genet 48:141–144PubMedCrossRefGoogle Scholar
- 9.Verkerk AJ, Schot R, Dumee B, Schellekens K, Swagemakers S, Bertoli-Avella AM, Lequin MH, Dudink J, Govaert P, van Zwol AL, Hirst J, Wessels MW, Catsman-Berrevoets C, Verheijen FW, de Graaff E, de Coo IF, Kros JM, Willemsen R, Willems PJ, van der Spek PJ, Mancini GM (2009) Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy. Am J Hum Genet 85:40–52PubMedCrossRefGoogle Scholar