title: Homozygous single base deletion in TUSC3 causes intellectual disability with developmental delay in an Omani family.
abstract: Intellectual disability (ID) is the term used to describe a diverse group of neurological conditions with congenital or juvenile onset, characterized by an IQ score of less than 70 and difficulties associated with limitations in cognitive function and adaptive behavior. The condition can be inherited or caused by environmental factors. The genetic forms are heterogeneous, with mutations in over 500 known genes shown to cause the disorder. We report a consanguineous Omani family in which multiple individuals have ID and developmental delay together with some variably present features including short stature, microcephaly, moderate facial dysmorphism, and congenital malformations of the toes or hands. Homozygosity mapping combined with whole exome next generation sequencing identified a novel homozygous single base pair deletion in TUSC3, c.222delA, p.R74 fs. The mutation segregates with the disease phenotype in a recessive manner and is absent in 60,706 unrelated individuals from various disease-specific and population genetic studies. TUSC3 mutations have been previously identified as causing either syndromic or non-syndromic ID in patients from France, Italy, Iran and Pakistan. This paper supports the previous clinical descriptions of the condition caused by TUSC3 mutations and describes the seventh family with mutations in this gene, thus contributing to the genetic spectrum of mutations. This is the first report of a family from the Arabian peninsula with this form of ID. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, United Kingdom.|School of Biomedical Sciences, University of Leeds, United Kingdom.|National Genetic Centre, Directorate General of Royal Hospital, Ministry of Health, Muscat, Oman.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al-Amri
authors.affiliation: Genetic and Developmental Medicine Clinic, Genetics Department, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Abeer Al
authors.initials: AA
authors.lastname: Saegh
authors.affiliation: Developmental Pediatric Unit, Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Watfa
authors.initials: W
authors.lastname: Al-Mamari
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, United Kingdom.|Department of Zoology, Faculty of Science, Benha University, Benha, Egypt.
authors.forename: Mohammed E
authors.initials: ME
authors.lastname: El-Asrag
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, United Kingdom.|School of Biomedical Sciences, University of Leeds, United Kingdom.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Ivorra
authors.affiliation: Academic Unit of Psychiatry and Behavioural Sciences, Leeds Institute of Health Sciences, University of Leeds, United Kingdom.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Cardno
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, United Kingdom.
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
authors.affiliation: School of Biomedical Sciences, University of Leeds, United Kingdom.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Clapcote
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, United Kingdom.
authors.forename: Manir
authors.initials: M
authors.lastname: Ali
mesh_terms: D003241:Consanguinity; D002658:Developmental Disabilities / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D005260:Female; D005602:France; D008040:Genetic Linkage; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D007492:Iran; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010154:Pakistan; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins
keywords: TUSC3; exome sequencing; intellectual disability