@article {913,
	title = {Missense variant contribution to USP9X-female syndrome.},
	journal = {NPJ Genom Med},
	volume = {5},
	year = {2020},
	month = {2020 Dec 09},
	pages = {53},
	abstract = {<p>USP9X is an X-chromosome gene that escapes X-inactivation. Loss or compromised function of USP9X leads to neurodevelopmental disorders in males and females. While males are impacted primarily by hemizygous partial loss-of-function missense variants, in females de novo heterozygous complete loss-of-function mutations predominate, and give rise to the clinically recognisable USP9X-female syndrome. Here we provide evidence of the contribution of USP9X missense and small in-frame deletion variants in USP9X-female syndrome also. We scrutinise the pathogenicity of eleven such variants, ten of which were novel. Combined application of variant prediction algorithms, protein structure modelling, and assessment under clinically relevant guidelines universally support their pathogenicity. The core phenotype of this cohort overlapped with previous descriptions of USP9X-female syndrome, but exposed heightened variability. Aggregate phenotypic information of 35 currently known females with predicted pathogenic variation in USP9X reaffirms the clinically recognisable USP9X-female syndrome, and highlights major differences when compared to USP9X-male associated neurodevelopmental disorders.</p>},
	issn = {2056-7944},
	doi = {10.1038/s41525-020-00162-9},
	author = {Jolly, Lachlan A and Parnell, Euan and Gardner, Alison E and Corbett, Mark A and P{\'e}rez-Jurado, Luis A and Shaw, Marie and Lesca, Gaetan and Keegan, Catherine and Schneider, Michael C and Griffin, Emily and Maier, Felicitas and Kiss, Courtney and Guerin, Andrea and Crosby, Kathleen and Rosenbaum, Kenneth and Tanpaiboon, Pranoot and Whalen, Sandra and Keren, Boris and McCarrier, Julie and Basel, Donald and Sadedin, Simon and White, Susan M and Delatycki, Martin B and Kleefstra, Tjitske and K{\"u}ry, S{\'e}bastien and Brusco, Alfredo and Sukarova-Angelovska, Elena and Trajkova, Slavica and Yoon, Sehoun and Wood, Stephen A and Piper, Michael and Penzes, Peter and Gecz, Jozef}
}
@article {464,
	title = {Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies.},
	journal = {Am J Hum Genet},
	volume = {102},
	year = {2018},
	month = {2018 05 03},
	pages = {985-994},
	abstract = {<p>N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of the N-terminal acetyltransferase A (NatA) complex. The auxiliary subunit of the NatA complex, NAA15, is the dimeric binding partner for NAA10. Through a genotype-first approach with whole-exome or genome sequencing (WES/WGS) and targeted sequencing analysis, we identified and phenotypically characterized 38 individuals from 33 unrelated families with 25 different de novo or inherited, dominantly acting likely gene disrupting (LGD) variants in NAA15. Clinical features of affected individuals with LGD variants in NAA15 include variable levels of intellectual disability, delayed speech and motor milestones, and autism spectrum disorder. Additionally, mild craniofacial dysmorphology, congenital cardiac anomalies, and seizures are present in some subjects. RNA analysis in cell lines from two individuals showed degradation of the transcripts with LGD variants, probably as a result of nonsense-mediated decay. Functional assays in yeast confirmed a deleterious effect for two of the LGD variants in NAA15. Further supporting a mechanism of haploinsufficiency, individuals with copy-number variant (CNV) deletions involving NAA15 and surrounding genes can present with mild intellectual disability, mild dysmorphic features, motor delays, and decreased growth. We propose that defects in NatA-mediated N-terminal acetylation (NTA) lead to variable levels of neurodevelopmental disorders in humans, supporting the importance of the NatA complex in normal human development.</p>},
	keywords = {Abnormalities, Multiple, Adolescent, Adult, Autism Spectrum Disorder, Cell Line, Child, Exons, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genetic Variation, Humans, Intellectual Disability, Male, Middle Aged, Mutation, N-Terminal Acetyltransferase A, N-Terminal Acetyltransferase E, Pedigree, Phenotype, RNA, Messenger, Saccharomyces cerevisiae},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2018.03.004},
	author = {Cheng, Hanyin and Dharmadhikari, Avinash V and Varland, Sylvia and Ma, Ning and Domingo, Deepti and Kleyner, Robert and Rope, Alan F and Yoon, Margaret and Stray-Pedersen, Asbj{\o}rg and Posey, Jennifer E and Crews, Sarah R and Eldomery, Mohammad K and Akdemir, Zeynep Coban and Lewis, Andrea M and Sutton, Vernon R and Rosenfeld, Jill A and Conboy, Erin and Agre, Katherine and Xia, Fan and Walkiewicz, Magdalena and Longoni, Mauro and High, Frances A and van Slegtenhorst, Marjon A and Mancini, Grazia M S and Finnila, Candice R and van Haeringen, Arie and den Hollander, Nicolette and Ruivenkamp, Claudia and Naidu, Sakkubai and Mahida, Sonal and Palmer, Elizabeth E and Murray, Lucinda and Lim, Derek and Jayakar, Parul and Parker, Michael J and Giusto, Stefania and Stracuzzi, Emanuela and Romano, Corrado and Beighley, Jennifer S and Bernier, Raphael A and K{\"u}ry, S{\'e}bastien and Nizon, Mathilde and Corbett, Mark A and Shaw, Marie and Gardner, Alison and Barnett, Christopher and Armstrong, Ruth and Kassahn, Karin S and Van Dijck, Anke and Vandeweyer, Geert and Kleefstra, Tjitske and Schieving, Jolanda and Jongmans, Marjolijn J and de Vries, Bert B A and Pfundt, Rolph and Kerr, Bronwyn and Rojas, Samantha K and Boycott, Kym M and Person, Richard and Willaert, Rebecca and Eichler, Evan E and Kooy, R Frank and Yang, Yaping and Wu, Joseph C and Lupski, James R and Arnesen, Thomas and Cooper, Gregory M and Chung, Wendy K and Gecz, Jozef and Stessman, Holly A F and Meng, Linyan and Lyon, Gholson J}
}
