| Autor: |
Usmani MA; Department of Otorhinolaryngology Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.; Department of Molecular Biology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan.; Jinnah Burn and Reconstructive Surgery Center, Allama Iqbal Medical College, University of Health Sciences, Lahore 54550, Pakistan., Ghaffar A; Department of Otorhinolaryngology Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.; Center of Excellence in Molecular Biology, University of the Punjab, Lahore 54500, Pakistan., Shahzad M; Department of Molecular Biology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan., Akram J; Department of Molecular Biology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan., Majeed AI; Department of Radiology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan., Malik K; Center of Excellence in Molecular Biology, University of the Punjab, Lahore 54500, Pakistan., Fatima K; Department of Applied Health Sciences, University of Management and Technology, Lahore 54500, Pakistan., Khan AA; Center of Excellence in Molecular Biology, University of the Punjab, Lahore 54500, Pakistan., Ahmed ZM; Department of Otorhinolaryngology Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.; Department of Molecular Biology and Biochemistry, School of Medicine, University of Maryland, Baltimore, MD 21201, USA., Riazuddin S; Department of Molecular Biology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan.; Jinnah Burn and Reconstructive Surgery Center, Allama Iqbal Medical College, University of Health Sciences, Lahore 54550, Pakistan., Riazuddin S; Department of Otorhinolaryngology Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.; Center of Excellence in Molecular Biology, University of the Punjab, Lahore 54500, Pakistan.; Department of Molecular Biology and Biochemistry, School of Medicine, University of Maryland, Baltimore, MD 21201, USA. |
| Abstrakt: |
Intellectual disability (ID), which affects around 2% to 3% of the population, accounts for 0.63% of the overall prevalence of neurodevelopmental disorders (NDD). ID is characterized by limitations in a person's intellectual and adaptive functioning, and is caused by pathogenic variants in more than 1000 genes. Here, we report a rare missense variant (c.350T>C; p.(Leu117Ser)) in HACE1 segregating with NDD syndrome with clinical features including ID, epilepsy, spasticity, global developmental delay, and psychomotor impairment in two siblings of a consanguineous Pakistani kindred. HACE1 encodes a HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1), which is involved in protein ubiquitination, localization, and cell division. HACE1 is also predicted to interact with several proteins that have been previously implicated in the ID phenotype in humans. The p.(Leu117Ser) variant replaces an evolutionarily conserved residue of HACE1 and is predicted to be deleterious by various in silico algorithms. Previously, eleven protein truncating variants of HACE1 have been reported in individuals with NDD. However, to our knowledge, p.(Leu117Ser) is the second missense variant in HACE1 found in an individual with NDD. |
