A Missense Variant in HACE1 Is Associated with Intellectual Disability, Epilepsy, Spasticity, and Psychomotor Impairment in a Pakistani Kindred

Author:

Usmani Muhammad A.123ORCID,Ghaffar Amama14,Shahzad Mohsin2,Akram Javed2,Majeed Aisha I.5,Malik Kausar4,Fatima Khushbakht6,Khan Asma A.4,Ahmed Zubair M.17ORCID,Riazuddin Sheikh23ORCID,Riazuddin Saima147

Affiliation:

1. Department of Otorhinolaryngology Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA

2. Department of Molecular Biology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan

3. Jinnah Burn and Reconstructive Surgery Center, Allama Iqbal Medical College, University of Health Sciences, Lahore 54550, Pakistan

4. Center of Excellence in Molecular Biology, University of the Punjab, Lahore 54500, Pakistan

5. Department of Radiology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan

6. Department of Applied Health Sciences, University of Management and Technology, Lahore 54500, Pakistan

7. Department of Molecular Biology and Biochemistry, School of Medicine, University of Maryland, Baltimore, MD 21201, USA

Abstract

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.

Funder

National Institutes of Health (NIH)—National Institute of Neurological Disorder and Stroke

Higher Education Commission Pakistan through NRPU project

Publisher

MDPI AG

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3