@article {756,
	title = {Congenital myasthenic syndrome with mild intellectual disability caused by a recurrent SLC25A1 variant.},
	journal = {Eur J Hum Genet},
	volume = {28},
	year = {2020},
	month = {2020 03},
	pages = {373-377},
	abstract = {<p>Congenital myasthenic syndromes (CMS) are a clinically and genetically heterogeneous group of disorders caused by mutations which lead to impaired neuromuscular transmission. SLC25A1 encodes a mitochondrial citrate carrier, associated mainly with the severe neurometabolic disease combined D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA). We previously reported a single family with a homozygous missense variant in SLC25A1 with a phenotype restricted to relatively mild CMS with intellectual disability, but to date no additional cases of this CMS subtype had been reported. Here, we performed whole exome sequencing (WES) in three additional and unrelated families presenting with CMS and mild intellectual disability to identify the underlying causative gene. The WES analysis revealed the presence of a homozygous c.740G>A; p.(Arg247Gln) missense SLC25A1 variant, the same SLC25A1 variant as identified in the original family with this phenotype. Electron microscopy of muscle from two cases revealed enlarged and accumulated mitochondria. Haplotype analysis performed in two unrelated families suggested that this variant is a result of recurrent mutation and not a founder effect. This suggests that p.(Arg247Gln) is associated with a relatively mild CMS phenotype with subtle mitochondrial abnormalities, while other variants in this gene cause more severe neurometabolic disease. In conclusion, the p.(Arg247Gln) SLC25A1 variant should be considered in patients presenting with a presynaptic CMS phenotype, particularly with accompanying intellectual disability.</p>},
	keywords = {Adult, Female, Haplotypes, Homozygote, Humans, Intellectual Disability, Male, Mitochondrial Proteins, Muscle, Skeletal, Mutation, Missense, Myasthenic Syndromes, Congenital, Organic Anion Transporters},
	issn = {1476-5438},
	doi = {10.1038/s41431-019-0506-2},
	author = {Balaraju, Sunitha and Topf, Ana and McMacken, Grace and Kumar, Veeramani Preethish and Pechmann, Astrid and Roper, Helen and Vengalil, Seena and Polavarapu, Kiran and Nashi, Saraswati and MAHjan, Niranjan Prakash and Barbosa, Ines A and Deshpande, Charu and Taylor, Robert W and Cossins, Judith and Beeson, David and Laurie, Steven and Kirschner, Janbernd and Horvath, Rita and McFarland, Robert and Nalini, Atchayaram and Lochm{\"u}ller, Hanns}
}
@article {755,
	title = {Severe neurodevelopmental disease caused by a homozygous TLK2 variant.},
	journal = {Eur J Hum Genet},
	volume = {28},
	year = {2020},
	month = {2020 03},
	pages = {383-387},
	abstract = {<p>A distinct neurodevelopmental phenotype characterised mainly by mild motor and language delay and facial dysmorphism, caused by heterozygous de novo or dominant variants in the TLK2 gene has recently been described. All cases reported carried either truncating variants located throughout the gene, or missense changes principally located at the C-terminal end of the protein mostly resulting in haploinsufficiency of TLK2. Through whole exome sequencing, we identified a homozygous missense variant in TLK2 in a patient showing more severe symptoms than those previously described, including cerebellar vermis hypoplasia and West syndrome. Both parents are heterozygous for the variant and clinically unaffected highlighting that recessive variants in TLK2 can also be disease causing and may act through a different pathomechanism.</p>},
	keywords = {Adult, Cerebellum, Child, Developmental Disabilities, Female, Heterozygote, Homozygote, Humans, Infant, Male, Mutation, Missense, Nervous System Malformations, Pedigree, Protein Kinases, Spasms, Infantile},
	issn = {1476-5438},
	doi = {10.1038/s41431-019-0519-x},
	author = {Topf, Ana and Oktay, Yavuz and Balaraju, Sunitha and Yilmaz, Elmasnur and Sonmezler, Ece and Yis, Uluc and Laurie, Steven and Thompson, Rachel and Roos, Andreas and MacArthur, Daniel G and Yaramis, Ahmet and G{\"u}ng{\"o}r, Serdal and Lochm{\"u}ller, Hanns and Hiz, Semra and Horvath, Rita}
}
