مورد إلكتروني
Rare variants in dynein heavy chain genes in two individuals with situs inversus and developmental dyslexia : a case report
| العنوان: | Rare variants in dynein heavy chain genes in two individuals with situs inversus and developmental dyslexia : a case report |
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| بيانات النشر: | KTH, Genteknologi KTH, Science for Life Laboratory, SciLifeLab KTH, Strukturell bioteknik Karolinska Inst, Dept Biosci & Nutr, Halsovagen 7, S-14183 Huddinge, Sweden. Karolinska Inst, Dept Biosci & Nutr, Hälsovagen 7, S-14183 Huddinge, Sweden.;Univ Helsinki, Stem Cells & Metab Res Program STEMM, Helsinki, Finland.;Folkhälsan Inst Genet, Helsinki, Finland. Karolinska Inst, Dept Womens & Childrens Hlth, Solna, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden. Karolinska Inst, Dept Biosci & Nutr, Hälsovagen 7, S-14183 Huddinge, Sweden. Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Inst, Sci Life Lab, Sci Pk, Solna, Sweden. Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.;Uppsala Univ Hosp, Dept Pathol, Uppsala, Sweden. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. Karolinska Inst, Dept Biosci & Nutr, Halsovagen 7, S-14183 Huddinge, Sweden.;Univ Helsinki, Stem Cells & Metab Res Program STEMM, Helsinki, Finland.;Guys Hosp, Kings Coll London, Sch Basic & Med Biosci, London, England. Karolinska Inst, Dept Med, Solnavagen 30, S-17176 Solna, Sweden. Springer 2020 |
| تفاصيل مُضافة: | Bieder, Andrea Einarsdottir, Elisabet Matsson, Hans Nilsson, Harriet Eisfeldt, Jesper Dragomir, Anca Paucar, Martin Granberg, Tobias Li, Tie-Qiang Lindstrand, Anna Kere, Juha Tapia-Paez, Isabel |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Background Developmental dyslexia (DD) is a neurodevelopmental learning disorder with high heritability. A number of candidate susceptibility genes have been identified, some of which are linked to the function of the cilium, an organelle regulating left-right asymmetry development in the embryo. Furthermore, it has been suggested that disrupted left-right asymmetry of the brain may play a role in neurodevelopmental disorders such as DD. However, it is unknown whether there is a common genetic cause to DD and laterality defects or ciliopathies. Case presentation Here, we studied two individuals with co-occurring situs inversus (SI) and DD using whole genome sequencing to identify genetic variants of importance for DD and SI. Individual 1 had primary ciliary dyskinesia (PCD), a rare, autosomal recessive disorder with oto-sino-pulmonary phenotype and SI. We identified two rare nonsynonymous variants in the dynein axonemal heavy chain 5 gene (DNAH5): a previously reported variant c.7502G > C; p.(R2501P), and a novel variant c.12043 T > G; p.(Y4015D). Both variants are predicted to be damaging. Ultrastructural analysis of the cilia revealed a lack of outer dynein arms and normal inner dynein arms. MRI of the brain revealed no significant abnormalities. Individual 2 had non-syndromic SI and DD. In individual 2, one rare variant (c.9110A > G;p.(H3037R)) in the dynein axonemal heavy chain 11 gene (DNAH11), coding for another component of the outer dynein arm, was identified. Conclusions We identified the likely genetic cause of SI and PCD in one individual, and a possibly significant heterozygosity in the other, both involving dynein genes. Given the present evidence, it is unclear if the identified variants also predispose to DD and further studies into the association between laterality, ciliopathies and DD are needed. QC 20200605 |
| مصطلحات الفهرس: | Developmental dyslexia, Situs inversus, Primary ciliary dyskinesia, L-R asymmetry defects, Whole genome sequencing, SNVs, Brain imaging, Medical Genetics, Medicinsk genetik, Article in journal, info:eu-repo/semantics/article, text |
| DOI: | 10.1186.s12881-020-01020-2 |
| URL: | BMC Medical Genetics, 1471-2350, 2020, 21:1 |
| الإتاحة: | Open access content. Open access content info:eu-repo/semantics/restrictedAccess |
| ملاحظة: | English |
| أرقام أخرى: | UPE oai:DiVA.org:kth-273898 0000-0003-3101-2285 0000-0001-7739-4405 doi:10.1186/s12881-020-01020-2 PMID 32357925 ISI:000531295000002 Scopus 2-s2.0-85084434047 1235053022 |
| المصدر المساهم: | UPPSALA UNIV LIBR From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1235053022 |
| قاعدة البيانات: | OAIster |
| DOI: | 10.1186.s12881-020-01020-2 |
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