@article {769,
	title = {Delineation of a Human Mendelian Disorder of the DNA Demethylation Machinery: TET3 Deficiency.},
	journal = {Am J Hum Genet},
	volume = {106},
	year = {2020},
	month = {2020 02 06},
	pages = {234-245},
	abstract = {<p>Germline pathogenic variants in chromatin-modifying enzymes are a common cause of pediatric developmental disorders. These enzymes catalyze reactions that regulate epigenetic inheritance via histone post-translational modifications and DNA methylation. Cytosine methylation (5-methylcytosine [5mC]) of DNA is the quintessential epigenetic mark, yet no human Mendelian disorder of DNA demethylation has yet been delineated. Here, we describe in detail a Mendelian disorder caused by the disruption of DNA demethylation. TET3 is a methylcytosine dioxygenase that initiates DNA demethylation during early zygote formation, embryogenesis, and neuronal differentiation and is intolerant to haploinsufficiency in mice and humans. We identify and characterize 11 cases of human TET3 deficiency in eight families with the common phenotypic features of intellectual disability and/or global developmental delay; hypotonia; autistic traits; movement disorders; growth abnormalities; and facial dysmorphism. Mono-allelic frameshift and nonsense variants in TET3 occur throughout the coding region. Mono-allelic and bi-allelic missense variants localize to conserved residues; all but one such variant occur within the catalytic domain, and most display hypomorphic function in an assay of catalytic activity. TET3 deficiency and other Mendelian disorders of the epigenetic machinery show substantial phenotypic overlap, including features of intellectual disability and abnormal growth, underscoring shared disease mechanisms.</p>},
	keywords = {Adult, Amino Acid Sequence, Autistic Disorder, Child, Child, Preschool, Developmental Disabilities, Dioxygenases, DNA Demethylation, Embryonic Development, Female, Gene Expression Regulation, Developmental, Growth Disorders, Humans, Infant, Male, Middle Aged, Movement Disorders, Pedigree, Protein Conformation, Sequence Homology, Young Adult},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2019.12.007},
	author = {Beck, David B and Petracovici, Ana and He, Chongsheng and Moore, Hannah W and Louie, Raymond J and Ansar, Muhammad and Douzgou, Sofia and Sithambaram, Sivagamy and Cottrell, Trudie and Santos-Cortez, Regie Lyn P and Prijoles, Eloise J and Bend, Renee and Keren, Boris and Mignot, Cyril and Nougues, Marie-Christine and {\~O}unap, Katrin and Reimand, Tiia and Pajusalu, Sander and Zahid, Muhammad and Saqib, Muhammad Arif Nadeem and Buratti, Julien and Seaby, Eleanor G and McWalter, Kirsty and Telegrafi, Aida and Baldridge, Dustin and Shinawi, Marwan and Leal, Suzanne M and Schaefer, G Bradley and Stevenson, Roger E and Banka, Siddharth and Bonasio, Roberto and Fahrner, Jill A}
}
@article {223,
	title = {NGLY1 mutation causes neuromotor impairment, intellectual disability, and neuropathy.},
	journal = {Eur J Med Genet},
	volume = {58},
	year = {2015},
	month = {2015 Jan},
	pages = {39-43},
	abstract = {<p>N-glycanase 1 (NGLY1) is a conserved enzyme that is responsible for the deglycosylation of misfolded N-glycosylated proteins in the cytoplasm prior to their proteasome-mediated degradation. Disruption of this degradation process has been associated with various neurologic diseases including amyotrophic lateral sclerosis and Parkinson{\textquoteright}s disease. Here, we describe two siblings with neuromotor impairment, apparent intellectual disability, corneal opacities, and neuropathy who were found to possess a novel homozygous frame-shift mutation due to a 4 base pair deletion in NGLY1 (c.1533_1536delTCAA, p.Asn511LysfsX51). We hypothesize that this mutation likely limits the capability of neuronal cells to respond to stress due to accumulation of misfolded proteins, thereby impairing their survival and resulting in progressive loss of neurological function. </p>},
	keywords = {Abnormalities, Multiple, Adolescent, Child, Corneal Opacity, Developmental Disabilities, Female, Frameshift Mutation, Genotype, Humans, Intellectual Disability, Male, Movement Disorders, Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase, Peripheral Nervous System Diseases},
	issn = {1878-0849},
	doi = {10.1016/j.ejmg.2014.08.008},
	author = {{\c C}a{\u g}layan, Ahmet Okay and Comu, Sinan and Baranoski, Jacob F and Parman, Yesim and Kaymak{\c c}alan, Hande and Akg{\"u}m{\"u}{\c s}, G{\"o}zde Tu{\u g}ce and Caglar, Caner and D{\"o}len, Duygu and Erson-Omay, Emine Zeynep and Harmanci, Akdes Serin and Mishra-Gorur, Ketu and Freeze, Hudson H and Yasuno, Katsuhito and Bilguvar, Kaya and G{\"u}nel, Murat}
}
