Protective inherited mutations in activity-dependent neuroprotective protein (ADNP): the good, the bad, and the ugly DOI
Illana Gozes, Shula Shazman, Eliezer Giladi

et al.

Genomic psychiatry :, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 7

Published: Nov. 14, 2024

Activity-dependent neuroprotective protein (ADNP), essential for brain formation/function, reveals multiple cytoplasmic and chromatin interacting sites. Computational modeling, alongside the Vineland Adaptive Behavior Scales, a leading instrument supporting diagnosis of intellectual/developmental disabilities, now revealed protective frame shift/stop mutation in ADNP. Thus, woman with inherited mutation, ADNP_Glu931Glyfs * 12 (VB), showed above average performance. Bioinformatics/ silico modeling indicated that while ADNP contains four 14-3-3 interaction sites (instrumental nuclear/cytoplasmic shuttling), an additional fifth site, implicating stronger associations. Furthermore, endogenous (investigational drug, davunetide) NAPVSIPQ (NAP) site was involved 12-14-3-3 interactions. In this respect, also enhanced ADNP-SH3 associations (another NAPVISP 354-361 aa on ADNP, critical cytoskeletal/cellular signaling). HB, 8-year-old VB's son, inheriting mother's further presented heterozygous pathogenic de novo p.Arg730Thrfs 5. However, comparison to carriers similar p.Arg730 (part autistic/intellectual disability syndrome), HB exhibited overall better 3 standard score 70–80 all measures, compared nominal 20 27-year-old subject 100 ± 15 norm, corroborating protection.

Language: Английский

Protective inherited mutations in activity-dependent neuroprotective protein (ADNP): the good, the bad, and the ugly DOI
Illana Gozes, Shula Shazman, Eliezer Giladi

et al.

Genomic psychiatry :, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 7

Published: Nov. 14, 2024

Activity-dependent neuroprotective protein (ADNP), essential for brain formation/function, reveals multiple cytoplasmic and chromatin interacting sites. Computational modeling, alongside the Vineland Adaptive Behavior Scales, a leading instrument supporting diagnosis of intellectual/developmental disabilities, now revealed protective frame shift/stop mutation in ADNP. Thus, woman with inherited mutation, ADNP_Glu931Glyfs * 12 (VB), showed above average performance. Bioinformatics/ silico modeling indicated that while ADNP contains four 14-3-3 interaction sites (instrumental nuclear/cytoplasmic shuttling), an additional fifth site, implicating stronger associations. Furthermore, endogenous (investigational drug, davunetide) NAPVSIPQ (NAP) site was involved 12-14-3-3 interactions. In this respect, also enhanced ADNP-SH3 associations (another NAPVISP 354-361 aa on ADNP, critical cytoskeletal/cellular signaling). HB, 8-year-old VB's son, inheriting mother's further presented heterozygous pathogenic de novo p.Arg730Thrfs 5. However, comparison to carriers similar p.Arg730 (part autistic/intellectual disability syndrome), HB exhibited overall better 3 standard score 70–80 all measures, compared nominal 20 27-year-old subject 100 ± 15 norm, corroborating protection.

Language: Английский

Citations

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