@Article{macau_mods_00005589,
  author = 	{Hussain, Syeda Iqra
		and Muhammad, Nazif
		and Khan, Niamatullah
		and Khan, Mobeen
		and Fardous, Fardous
		and Tahir, Raheel
		and Yasin, Muhammad
		and Khan, Sher Alam
		and Saleha, Shamim
		and Muhammad, Noor
		and Wasif, Naveed
		and Khan, Saadullah},
  title = 	{Molecular insight into CREBBP and TANGO2 variants causing intellectual disability},
  journal = 	{The journal of gene medicine : a cross-disciplinary journal of research on the science of gene transfer and its clinical applications},
  year = 	{2024},
  publisher = 	{Wiley},
  address = 	{Chichester},
  volume = 	{26},
  number = 	{1},
  pages = 	{e3591},
  keywords = 	{Humans; Rubinstein-Taybi Syndrome; Rhabdomyolysis; Phenotype; Mutation; Mutation, Missense; CREB-Binding Protein; Intellectual Disability; Bioinformatics; Molecular genetics; Neurology},
  abstract = 	{Background Intellectual disability (ID) can be associated with different syndromes such as Rubinstein-Taybi syndrome (RSTS) and can also be related to conditions such as metabolic encephalomyopathic crises, recurrent,with rhabdomyolysis, cardiac arrhythmias and neurodegeneration. Rare congenital RSTS1 (OMIM 180849) is characterized by mental and growth retardation, significant and duplicated distal phalanges of thumbs and halluces, facial dysmorphisms, and an elevated risk of malignancies. Microdeletions and point mutations in the CREB-binding protein (CREBBP) gene, located at 16p13.3, have been reported to cause RSTS. By contrast, TANGO2-related metabolic encephalopathy and arrhythmia (TRMEA) is a rare metabolic condition that causes repeated metabolic crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias and encephalopathy with cognitive decline. Results In the present study, two families (A and B) exhibiting various forms of IDs were enrolled. In Family A, exome sequencing revealed a novel missense variant (NM 004380.3: c.4571A>G; NP{\_}004371.2: p.Lys1524Arg) in the CREBBP gene, whereas, in Family B, a splice site variant (NM 152906.7: c.605{\thinspace}+{\thinspace}1G>A) in the TANGO2 gene was identified. Sanger sequencing of both variants confirmed their segregation with ID in both families. The in silico tools verified the aberrant changes in the CREBBP protein structure. Wild-type and mutant CREBBP protein structures were superimposed and conformational changes were observed likely altering the protein function. Conclusions RSTS and TRMEA are exceedingly rare disorders for which specific clinical characteristics have been clearly established, but more investigations are underway and required. Multicenter studies are needed to increase our understanding of the clinical phenotypes, mainly showing the genotype-phenotype associations.},
  issn = 	{1099-498X},
  doi = 	{10.1002/jgm.3591},
  url = 	{https://macau.uni-kiel.de/receive/macau_mods_00005589},
  url = 	{https://doi.org/10.1002/jgm.3591},
  url = 	{http://www.ncbi.nlm.nih.gov/pubmed/37721116},
  file = 	{:https://macau.uni-kiel.de/servlets/MCRFileNodeServlet/macau_derivate_00007024/The%20Journal%20of%20Gene%20Medicine%20-%202023%20-%20Hussain%20-%20Molecular%20insight%20into%20CREBBP%20and%20TANGO2%20variants%20causing%20intellectual.pdf:PDF},
  language = 	{en}
}