A frameshift mutation of ERLIN2 in recessive intellectual disability, motor dysfunction and multiple joint contractures


Yildirim Y., Orhan E., Iseri S. A. U., Serdaroglu-Oflazer P., KARA B., Solakoglu S., ...Daha Fazla

HUMAN MOLECULAR GENETICS, cilt.20, sa.10, ss.1886-1892, 2011 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 20 Sayı: 10
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1093/hmg/ddr070
  • Dergi Adı: HUMAN MOLECULAR GENETICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1886-1892
  • İstanbul Üniversitesi Adresli: Evet

Özet

We present a family afflicted with a novel autosomal recessive disease characterized by progressive intellectual disability, motor dysfunction and multiple joint contractures. No pathology was found by cranial imaging, electromyography and muscle biopsy, but electron microscopy in leukocytes revealed large vacuoles containing flocculent material. We mapped the disease gene by SNP genome scan and linkage analysis to an similar to 0.80 cM and 1 Mb region at 8p11.23 with a multipoint logarithm of odds (LOD) score of 12. By candidate gene approach, we identified a homozygous two-nucleotide insertion in ERLIN2, predicted to lead to the truncation of the protein by about 20%. The gene encodes endoplasmic reticulum (ER) lipid raft-associated protein 2 that mediates the ER-associated degradation of activated inositol 1,4,5-trisphosphate receptors and other substrates.