dc.contributor.author | Mercan, Sevcan | |
dc.contributor.author | Akcakaya, Nihan Hande | |
dc.contributor.author | Salman, Baris | |
dc.contributor.author | Yapici, Zuhal | |
dc.contributor.author | Ozbek, Ugur | |
dc.contributor.author | Ugur Iseri, Sibel Aylin | |
dc.date.accessioned | 2024-02-04T13:29:38Z | |
dc.date.available | 2024-02-04T13:29:38Z | |
dc.date.issued | 2023 | |
dc.identifier.issn | 1976-9571 | |
dc.identifier.issn | 2092-9293 | |
dc.identifier.uri | https://doi.org/10.1007/s13258-022-01344-8 | |
dc.identifier.uri | http://hdl.handle.net/11446/4707 | |
dc.description.abstract | Background Syndromic intellectual disability (ID) with accompanying primary microcephaly is a group of rare neurodevelopmental disorders exhibiting extreme genetic and clinical heterogeneity. This layered heterogeneity can partially be resolved by unbiased genetic approaches targeting the genome with next generation sequencing (NGS) technologies, including exome sequencing (ES). Objective This study was performed to dissect the clinical and genetic features in five distinct IDM cases. Methods Singleton or trio ES approach followed by in-depth variant analysis using alternative inheritance models was performed. Results We have identified biallelic loss of function variants in genes WDR62 and AP4M1 in three families, together with de novo missense variants in genes SOX11 and TRIO in two families. ES based haplotype analysis in two cases upon identification of an identical WDR62 variant in the homozygous state in two cases was suggestive of a small shared haplotype of 0.1 Mb. Additionally, we have shown a paternal origin for the de novo variant in TRIO via a polymorphic tag SNP, which enlightens the mutational mechanism for this variant. Conclusion In populations with high parental consanguinity, an autosomal recessive inheritance pattern for data analysis is usually the most obvious choice. Therefore, heterozygous variants may be overlooked in standard NGS analyses in consanguineous families. Our findings underlie the importance of using multiple inheritance models in NGS data analysis. | en_US |
dc.description.sponsorship | Scientific Research Projects Coordination Unit of Istanbul University [TDK-2017-25704, TSA-2018-27512]; Turkish Academy of Sciences | en_US |
dc.description.sponsorship | The authors are grateful to the patients and their relatives for their participation in this study. This work was supported by the grants of Scientific Research Projects Coordination Unit of Istanbul University (grant reference numbers TDK-2017-25704 and TSA-2018-27512). We also thank to Turkish Academy of Sciences for the 2019 Distinguished Young Scientist Award to SAUI. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Springer | en_US |
dc.relation.ispartof | Genes & Genomics | en_US |
dc.identifier.doi | 10.1007/s13258-022-01344-8 | |
dc.rights | info:eu-repo/semantics/closedAccess | en_US |
dc.subject | Microcephaly | en_US |
dc.subject | Intellectual disability | en_US |
dc.subject | Exome sequencing (ES) | en_US |
dc.subject | Parent of origin effect | en_US |
dc.subject | WDR62 | en_US |
dc.subject | TRIO | en_US |
dc.subject | SOX11 | en_US |
dc.title | Clinical and genetic analyses in syndromic intellectual disability with primary microcephaly reveal biallelic and de novo variants in patients with parental consanguinity | en_US |
dc.type | article | en_US |
dc.department | DBÜ | en_US |
dc.identifier.issue | 1 | en_US |
dc.identifier.volume | 45 | en_US |
dc.identifier.startpage | 13 | en_US |
dc.identifier.endpage | 21 | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.department-temp | [Mercan, Sevcan; Akcakaya, Nihan Hande; Salman, Baris; Ugur Iseri, Sibel Aylin] Istanbul Univ, Aziz Sancar Inst Expt Med, Dept Genet, TR-34093 Istanbul, Turkey; [Mercan, Sevcan; Akcakaya, Nihan Hande; Salman, Baris] Istanbul Univ, Grad Sch Hlth Sci, Istanbul, Turkey; [Mercan, Sevcan] Kafkas Univ, Fac Engn & Architecture, Dept Bioengn, Kars, Turkey; [Akcakaya, Nihan Hande] Demiroglu Bilim Univ, Fac Med, Dept Neurol, Istanbul, Turkey; [Akcakaya, Nihan Hande] Spastic Childrens Fdn Turkey, Istanbul, Turkey; [Yapici, Zuhal] Istanbul Univ, Istanbul Fac Med, Dept Neurol, Istanbul, Turkey; [Ozbek, Ugur] Acibadem Mehmet Ali Aydinlar Univ, Fac Med, Dept Med Genet, Istanbul, Turkey | en_US |
dc.authorid | Akcakaya, Nihan Hande/0000-0001-8414-4017 | |
dc.authorid | Salman, Barış/0000-0002-7657-8576 | |
dc.authorid | Ugur Iseri, Sibel Aylin/0000-0002-5790-6853 | |
dc.identifier.pmid | 36371492 | en_US |
dc.identifier.scopus | 2-s2.0-85141741995 | en_US |
dc.identifier.wos | WOS:000882351800003 | en_US |
dc.authorwosid | Akcakaya, Nihan Hande/GQP-7316-2022 | |
dc.authorwosid | Salman, Barış/AEG-0803-2022 | |