{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T18:00:30Z","timestamp":1777312830462,"version":"3.51.4"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004054","name":"King Abdulaziz University","doi-asserted-by":"publisher","award":["G:582-247-1443"],"award-info":[{"award-number":["G:582-247-1443"]}],"id":[{"id":"10.13039\/501100004054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Salt and pepper developmental regression syndrome (SPDRS) is an autosomal recessive disorder characterized by epilepsy, profound intellectual disability, choreoathetosis, scoliosis, and dermal pigmentation along with dysmorphic facial features. GM3 synthase deficiency is due to any pathogenic mutation in the ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5 (ST3GAL5) gene, which encodes the sialyltransferase enzyme that synthesizes ganglioside GM3. In this study, the Whole Exome Sequencing (WES) results presented a novel homozygous pathogenic variant, NM_003896.3:c.221T&gt;A (p.Val74Glu), in the exon 3 of the ST3GAL5 gene. causing SPDRS with epilepsy, short stature, speech delay, and developmental delay in all three affected members of the same Saudi family. The results of the WES sequencing were further validated using Sanger sequencing analysis. For the first time, we are reporting SPDRS in a Saudi family showing phenotypic features similar to other reported cases. This study further adds to the literature and explains the role of the ST3GAL5 gene, which plays an important role, and any pathogenic variants that may cause the GM3 synthase deficiency that leads to the disease. This study would finally enable the creation of a database of the disease that provides a base for understanding the important and critical genomic regions that will help control intellectual disability and epilepsy in Saudi patients.<\/jats:p>","DOI":"10.3390\/genes14020354","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T07:34:41Z","timestamp":1675064081000},"page":"354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Whole Exome Sequencing Reveals a Novel Homozygous Variant in the Ganglioside Biosynthetic Enzyme, ST3GAL5 Gene in a Saudi Family Causing Salt and Pepper Syndrome"],"prefix":"10.3390","volume":"14","author":[{"given":"Angham Abdulrhman","family":"Abdulkareem","sequence":"first","affiliation":[{"name":"Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Faculty of Science, Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bader H.","family":"Shirah","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, King Faisal Specialist Hospital & Research Centre, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Imran","family":"Naseer","sequence":"additional","affiliation":[{"name":"Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1093\/hmg\/ddt434","article-title":"A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt & pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation","volume":"23","author":"Boccuto","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Paprocka, J., Jezela-Stanek, A., Tylki-Szyma\u0144ska, A., and Grunewald, S. (2021). Congenital disorders of glycosylation from a neurological perspective. Brain Sci., 11.","DOI":"10.3390\/brainsci11010088"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/bs.pmbts.2017.10.004","article-title":"Biology of GM3 Ganglioside","volume":"156","author":"Inokuchi","year":"2018","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/bs.pmbts.2018.01.001","article-title":"Congenital Disorders of Ganglioside Biosynthesis","volume":"156","author":"Li","year":"2018","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ymgme.2019.01.013","article-title":"Recessive GM3 synthase deficiency: Natural history, biochemistry, and therapeutic frontier","volume":"126","author":"Bowser","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/ng1460","article-title":"Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase","volume":"36","author":"Simpson","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/ejhg.2012.202","article-title":"Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency","volume":"21","author":"Fragaki","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1002\/ajmg.a.37773","article-title":"GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: Masquerading as Rett syndrome-like phenotype","volume":"170","author":"Lee","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/cge.12703","article-title":"Early growth and development impairments in patients with ganglioside GM3 synthase deficiency","volume":"89","author":"Wang","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0378-1119(01)00595-9","article-title":"Genomic structure of human GM3 synthase gene (hST3Gal V) and identification of mRNA isoforms in the 5-prime-untranslated region","volume":"273","author":"Kim","year":"2001","journal-title":"Gene"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1073\/pnas.0635898100","article-title":"Enhanced insulin sensitivity in mice lacking ganglioside GM3","volume":"100","author":"Yamashita","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9483","DOI":"10.1073\/pnas.0903279106","article-title":"Mice lacking gan-glioside GM3 synthase exhibit complete hearing loss due to selective degeneration of the organ of Corti","volume":"106","author":"Yoshikawa","year":"2009","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/13816810600862626","article-title":"Etiology of Vision Loss in Ganglioside GM3 Synthase Deficiency","volume":"27","author":"Farukhi","year":"2006","journal-title":"Ophthalmic Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1002\/ajmg.a.35826","article-title":"Cutaneous dyspigmentation in patients with ganglioside GM3 syn-thase deficiency","volume":"161","author":"Wang","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s10072-018-3626-5","article-title":"A novel homozygous nonsense mutation in CCDC88A gene cause PEHO-like syndrome in consanguineous Saudi family","volume":"40","author":"Abdulkareem","year":"2018","journal-title":"Neurol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fgene.2020.00014","article-title":"Exome Analysis Identified Novel Homozygous Splice Site Donor Alteration in NT5C2 Gene in a Saudi Family Associated With Spastic Diplegia Cerebral Palsy, Developmental Delay, and Intellectual Disability","volume":"11","author":"Naseer","year":"2020","journal-title":"Front. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"984","DOI":"10.3389\/fped.2020.627122","article-title":"Whole Exome Sequencing Identifies Three Novel Mutations in the ASPM Gene From Saudi Families Leading to Primary Microcephaly","volume":"8","author":"Naseer","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e20171377","DOI":"10.1542\/peds.2017-1377","article-title":"Anxiety and Mood Disorder in Children With Autism Spectrum Disorder and ADHD","volume":"141","author":"Marvin","year":"2018","journal-title":"Pediatrics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ymgme.2017.04.002","article-title":"A multi-center clinical exome study in unselected cohorts from a consanguineous population of Saudi Arabia demonstrated a high diagnostic yield","volume":"121","author":"Alfares","year":"2017","journal-title":"Mol. Genet Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"572965","DOI":"10.3389\/fnins.2020.572965","article-title":"Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications","volume":"14","author":"Sipione","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.1016\/j.jmb.2016.05.020","article-title":"Gangliosides of the Vertebrate Nervous System","volume":"428","author":"Schnaar","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ymgme.2018.06.014","article-title":"Diseases of ganglioside biosynthesis: An expanding group of congenital disorders of glycosylation","volume":"124","author":"Trinchera","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_24","first-page":"6","article-title":"\u2018Salt-And-Pepper\u2019 pigmentary changes with severe mental retardation: A new neu-rocutaneous syndrome?","volume":"2","author":"Saul","year":"1983","journal-title":"Proc. Greenwood Genet Ctr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41439-021-00164-8","article-title":"A novel frameshift pathogenic variant in ST3GAL5 causing salt and pepper developmental regression syndrome (Spdrs): A case report","volume":"8","author":"Manoochehri","year":"2021","journal-title":"Hum. Genome Var."},{"key":"ref_26","first-page":"2629","article-title":"Map of autosomal recessive genetic disorders in Saudi Arabia: Concepts and future directions","volume":"158","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.ajhg.2012.10.015","article-title":"Deleterious- and disease-allele prevalence in healthy individuals: Insights from current predictions, mutation databases, and population-scale resequencing","volume":"91","author":"Xue","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.1215040","article-title":"A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes","volume":"335","author":"MacArthur","year":"2012","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1056\/NEJMoa1306555","article-title":"Clinical whole-exome sequencing for the diagnosis of mendelian disorders","volume":"369","author":"Yang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1001\/jama.2014.14604","article-title":"Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders","volume":"312","author":"Lee","year":"2014","journal-title":"JAMA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1001\/jama.2014.14601","article-title":"Molecular findings among patients referred for clinical whole-exome sequencing","volume":"312","author":"Yang","year":"2014","journal-title":"JAMA"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/2\/354\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:19:48Z","timestamp":1760120388000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/2\/354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,30]]},"references-count":31,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["genes14020354"],"URL":"https:\/\/doi.org\/10.3390\/genes14020354","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,30]]}}}