@article {28,
	title = {De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome.},
	journal = {Am J Hum Genet},
	volume = {99},
	year = {2016},
	month = {2016 Sep 01},
	pages = {711-719},
	abstract = {<p>The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and~HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development.</p>},
	keywords = {Animals, Brain, Developmental Disabilities, DNA-Binding Proteins, Eye Abnormalities, Female, Genes, Essential, Haploinsufficiency, Head, Heterozygote, Humans, Intellectual Disability, Male, Metabolic Diseases, Minor Histocompatibility Antigens, Mutation, Pedigree, RNA Splicing, RNA, Messenger, Spine, Syndrome, Zebrafish},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2016.06.029},
	author = {Kim, Jung-Hyun and Shinde, Deepali N and Reijnders, Margot R F and Hauser, Natalie S and Belmonte, Rebecca L and Wilson, Gregory R and Bosch, Dani{\"e}lle G M and Bubulya, Paula A and Shashi, Vandana and Petrovski, Slav{\'e} and Stone, Joshua K and Park, Eun Young and Veltman, Joris A and Sinnema, Margje and Stumpel, Connie T R M and Draaisma, Jos M and Nicolai, Joost and Yntema, Helger G and Lindstrom, Kristin and de Vries, Bert B A and Jewett, Tamison and Santoro, Stephanie L and Vogt, Julie and Bachman, Kristine K and Seeley, Andrea H and Krokosky, Alyson and Turner, Clesson and Rohena, Luis and Hempel, Maja and Kort{\"u}m, Fanny and Lessel, Davor and Neu, Axel and Strom, Tim M and Wieczorek, Dagmar and Bramswig, Nuria and Laccone, Franco A and Behunova, Jana and Rehder, Helga and Gordon, Christopher T and Rio, Marl{\`e}ne and Romana, Serge and Tang, Sha and El-Khechen, Dima and Cho, Megan T and McWalter, Kirsty and Douglas, Ganka and Baskin, Berivan and Begtrup, Amber and Funari, Tara and Schoch, Kelly and Stegmann, Alexander P A and Stevens, Servi J C and Zhang, Dong-Er and Traver, David and Yao, Xu and MacArthur, Daniel G and Brunner, Han G and Mancini, Grazia M and Myers, Richard M and Owen, Laurie B and Lim, Ssang-Taek and Stachura, David L and Vissers, Lisenka E L M and Ahn, Eun-Young Erin}
}
@article {184,
	title = {Cerebral visual impairment and intellectual disability caused by PGAP1 variants.},
	journal = {Eur J Hum Genet},
	volume = {23},
	year = {2015},
	month = {2015 Dec},
	pages = {1689-93},
	abstract = {<p>Homozygous variants in PGAP1 (post-GPI attachment to proteins 1) have recently been identified in two families with developmental delay, seizures and/or spasticity. PGAP1 is a member of the glycosylphosphatidylinositol anchor biosynthesis and remodeling pathway and defects in this pathway are a subclass of congenital disorders of glycosylation. Here we performed whole-exome sequencing in an individual with cerebral visual impairment (CVI), intellectual disability (ID), and factor XII deficiency and revealed compound heterozygous variants in PGAP1, c.274_276del (p.(Pro92del)) and c.921_925del (p.(Lys308Asnfs*25)). Subsequently, PGAP1-deficient Chinese hamster ovary (CHO)-cell lines were transfected with either mutant or wild-type constructs and their sensitivity to phosphatidylinositol-specific phospholipase C (PI-PLC) treatment was measured. The mutant constructs could not rescue the PGAP1-deficient CHO cell lines resistance to PI-PLC treatment. In addition, lymphoblastoid cell lines (LCLs) of the affected individual showed no sensitivity to PI-PLC treatment, whereas the LCLs of the heterozygous carrier parents were partially resistant. In conclusion, we report novel PGAP1 variants in a boy with CVI and ID and a proven functional loss of PGAP1 and show, to our knowledge, for the first time this genetic association with CVI. </p>},
	keywords = {Animals, Cell Line, Tumor, Child, CHO Cells, Cricetinae, Cricetulus, Humans, Intellectual Disability, Male, Membrane Proteins, Mutation, Phosphoinositide Phospholipase C, Phosphoric Monoester Hydrolases, Syndrome, Vision Disorders, Visual Perception},
	issn = {1476-5438},
	doi = {10.1038/ejhg.2015.42},
	author = {Bosch, Dani{\"e}lle G M and Boonstra, F Nienke and Kinoshita, Taroh and Jhangiani, Shalini and de Ligt, Joep and Cremers, Frans P M and Lupski, James R and Murakami, Yoshiko and de Vries, Bert B A}
}
