@article {815,
	title = {Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions.},
	journal = {J Inherit Metab Dis},
	volume = {43},
	year = {2020},
	month = {2020 11},
	pages = {1333-1348},
	abstract = {<p>Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-N-acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13-deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13. This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals.</p>},
	issn = {1573-2665},
	doi = {10.1002/jimd.12290},
	author = {Ng, Bobby G and Eklund, Erik A and Shiryaev, Sergey A and Dong, Yin Y and Abbott, Mary-Alice and Asteggiano, Carla and Bamshad, Michael J and Barr, Eileen and Bernstein, Jonathan A and Chelakkadan, Shabeed and Christodoulou, John and Chung, Wendy K and Ciliberto, Michael A and Cousin, Janice and Gardiner, Fiona and Ghosh, Suman and Graf, William D and Grunewald, Stephanie and Hammond, Katherine and Hauser, Natalie S and Hoganson, George E and Houck, Kimberly M and Kohler, Jennefer N and Morava, Eva and Larson, Austin A and Liu, Pengfei and Madathil, Sujana and McCormack, Colleen and Meeks, Naomi J L and Miller, Rebecca and Monaghan, Kristin G and Nickerson, Deborah A and Palculict, Timothy Blake and Papazoglu, Gabriela Magali and Pletcher, Beth A and Scheffer, Ingrid E and Schenone, Andrea Beatriz and Schnur, Rhonda E and Si, Yue and Rowe, Leah J and Serrano Russi, Alvaro H and Russo, Rossana Sanchez and Thabet, Farouq and Tuite, Allysa and Villanueva, Mar{\'\i}a Mercedes and Wang, Raymond Y and Webster, Richard I and Wilson, Dorcas and Zalan, Alice and Wolfe, Lynne A and Rosenfeld, Jill A and Rhodes, Lindsay and Freeze, Hudson H}
}
@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}
}
