Mutations in the gene encoding the sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation

Patrick S. Tarpey, Claire Stevens, Jon Teague, Sarah Edkins, Sarah O'Meara, Tim Avis, Syd Barthorpe, Gemma Buck, Adam Butler, Jennifer Cole, Ed Dicks, Kristian Gray, Kelly Halliday, Rachel Harrison, Katy Hills, Jonathon Hinton, David Jones, Andrew Menzies, Tatiana Mironenko, Janet PerryKeiran Raine, David Richardson, Rebecca Shepherd, Alexandra Small, Calli Tofts, Jennifer Varian, Sofie West, Sara Widaa, Andy Yates, Rachael Catford, Julia Butler, Uma Mallya, Jenny Moon, Ying Luo, Huw Dorkins, Deborah Thompson, Douglas F. Easton, Richard Wooster, Martin Bobrow, Nancy Carpenter, Richard J. Simensen, Charles E. Schwartz, Roger E. Stevenson, Gillian Turner, Michael Partington, Jozef Gecz, Michael R. Stratton, P. Andrew Futreal, F. Lucy Raymond

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In a systematic sequencing screen of the coding exons of the X chromosome in 250 families with X-linked mental retardation (XLMR), we identified two nonsense mutations and one consensus splice-site mutation in the AP1S2 gene on Xp22 in three families. Affected individuals in these families showed mild-to-profound mental retardation. Other features included hypotonia early in life and delay in walking. AP1S2 encodes an adaptin protein that constitutes part of the adaptor protein complex found at the cytoplasmic face of coated vesicles located at the Golgi complex. The complex mediates the recruitment of clathrin to the vesicle membrane. Aberrant endocytic processing through disruption of adaptor protein complexes is likely to result from the AP1S2 mutations identified in the three XLMR-affected families, and such defects may plausibly cause abnormal synaptic development and function. AP1S2 is the first reported XLMR gene that encodes a protein directly involved in the assembly of endocytic vesicles.

Original languageEnglish
Pages (from-to)1119-1124
Number of pages6
JournalAmerican Journal of Human Genetics
Issue number6
Publication statusPublished - Dec 2006
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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