000K  utf8
1100  $c2024
1500  eng
2050  urn:nbn:de:gbv:8:3-2025-00068-9
2051  10.1002/jgm.3591
3000  Hussain, Syeda Iqra
3010  Fardous, Fardous
3010  Khan, Mobeen
3010  Khan, Niamatullah
3010  Khan, Saadullah
3010  Khan, Sher Alam
3010  Muhammad, Nazif
3010  Muhammad, Noor
3010  Saleha, Shamim
3010  Tahir, Raheel
3010  Wasif, Naveed
3010  Yasin, Muhammad
4000  Molecular insight into CREBBP and TANGO2 variants causing intellectual disability$hWiley  [Hussain, Syeda Iqra]
4030  $nWiley
4209  Background Intellectual disability (ID) can be associated with different syndromes such as Rubinstein-Taybi syndrome (RSTS) and can also be related to conditions such as metabolic encephalomyopathic crises, recurrent,with rhabdomyolysis, cardiac arrhythmias and neurodegeneration. Rare congenital RSTS1 (OMIM 180849) is characterized by mental and growth retardation, significant and duplicated distal phalanges of thumbs and halluces, facial dysmorphisms, and an elevated risk of malignancies. Microdeletions and point mutations in the CREB-binding protein (CREBBP) gene, located at 16p13.3, have been reported to cause RSTS. By contrast, TANGO2-related metabolic encephalopathy and arrhythmia (TRMEA) is a rare metabolic condition that causes repeated metabolic crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias and encephalopathy with cognitive decline. Results In the present study, two families (A and B) exhibiting various forms of IDs were enrolled. In Family A, exome sequencing revealed a novel missense variant (NM 004380.3: c.4571A>G; NP_004371.2: p.Lys1524Arg) in the CREBBP gene, whereas, in Family B, a splice site variant (NM 152906.7: c.605 + 1G>A) in the TANGO2 gene was identified. Sanger sequencing of both variants confirmed their segregation with ID in both families. The in silico tools verified the aberrant changes in the CREBBP protein structure. Wild-type and mutant CREBBP protein structures were superimposed and conformational changes were observed likely altering the protein function. Conclusions RSTS and TRMEA are exceedingly rare disorders for which specific clinical characteristics have been clearly established, but more investigations are underway and required. Multicenter studies are needed to increase our understanding of the clinical phenotypes, mainly showing the genotype-phenotype associations.
4950  https://doi.org/10.1002/jgm.3591$xR$3Volltext$534
4950  https://nbn-resolving.org/urn:nbn:de:gbv:8:3-2025-00068-9$xR$3Volltext$534
4961  https://macau.uni-kiel.de/receive/macau_mods_00005589
5051  610
5550  Bioinformatics
5550  CREB-Binding Protein
5550  Humans
5550  Intellectual Disability
5550  Molecular genetics
5550  Mutation
5550  Mutation, Missense
5550  Neurology
5550  Phenotype
5550  Rhabdomyolysis
5550  Rubinstein-Taybi Syndrome