Johanna Lehtonen

• Lehtonen, Johanna; Sulonen, Anna-Maija; Almusa, Henrikki; Lehtokari, Vilma-Lotta; Johari, Mridul & Palva, Aino [Show all 14 contributors for this article] (2024). Haplotype information of large neuromuscular disease genes provided by linked-read sequencing has a potential to increase diagnostic yield. Scientific Reports. ISSN 2045-2322. 14(1). doi: 10.1038/s41598-024-54866-4.
• Pelin, Katarina; Sagath, Lydia; Lehtonen, Johanna; Kiiski, Kirsi; Tynninen, Olli & Paetau, Anders [Show all 10 contributors for this article] (2023). Novel Compound Heterozygous Splice-Site Variants in TPM3 Revealed by RNA Sequencing in a Patient with an Unusual Form of Nemaline Myopathy: A Case Report. Journal of Neuromuscular Diseases. ISSN 2214-3599. 10(5), p. 977–984. doi: 10.3233/JND-230026. Full text in Research Archive
• Kaustio, Meri; Nayebzadeh, Naemeh; Hinttala, Reetta; Tapiainen, Terhi; Åström, Pirjo & Mamia, Katariina Aino Inkeri [Show all 37 contributors for this article] (2021). Loss of DIAPH1 causes SCBMS, combined immunodeficiency, and mitochondrial dysfunction. Journal of Allergy and Clinical Immunology. ISSN 0091-6749. 148(2), p. 599–611. doi: 10.1016/j.jaci.2020.12.656. Full text in Research Archive
• Hakonen, Anna H; Lehtonen, Johanna; Kivirikko, Sirpa; Keski‐Filppula, Riikka; Moilanen, Jukka & Kivisaari, Reetta [Show all 11 contributors for this article] (2020). Recessive MYH3 variants cause “Contractures, pterygia, and variable skeletal fusions syndrome 1B” mimicking Escobar variant multiple pterygium syndrome. American Journal of Medical Genetics. Part A. ISSN 1552-4825. 182(11), p. 2605–2610. doi: 10.1002/ajmg.a.61836. Show summary

  The multiple pterygium syndromes (MPS) are rare disorders with disease severity ranging from lethal to milder forms. The nonlethal Escobar variant MPS (EVMPS) is characterized by multiple pterygia and arthrogryposis, as well as various additional features including congenital anomalies. The genetic etiology of EVMPS is heterogeneous and the diagnosis has been based either on the detection of pathogenic CHRNG variants (~23% of patients), or suggestive clinical features. We describe four patients with a clinical suspicion of EVMPS who manifested with multiple pterygia, mild flexion contractures of several joints, and vertebral anomalies. We revealed recessively inherited MYH3 variants as the underlying cause in all patients: two novel variants, c.1053C>G, p.(Tyr351Ter) and c.3102+5G>C, as compound heterozygous with the hypomorphic MYH3 variant c.‐9+1G>A. Recessive MYH3 variants have been previously associated with spondylocarpotarsal synostosis syndrome. Our findings now highlight multiple pterygia as an important feature in patients with recessive MYH3 variants. Based on all patients with recessive MYH3 variants reported up to date, we consider that this disease entity should be designated as “Contractures, pterygia, and variable skeletal fusions syndrome 1B,” as recently suggested by OMIM. Our findings underline the importance of analyzing MYH3 in the differential diagnosis of EVMPS, particularly as the hypomorphic MYH3 variant might remain undetected by routine exome sequencing.

• Partanen, Terhi; Chen, Jie; Lehtonen, Johanna; Kuismin, Outi; Rusanen, Harri & Vapalahti, Olli [Show all 21 contributors for this article] (2020). Heterozygous TLR3 Mutation in Patients with Hantavirus Encephalitis. Journal of Clinical Immunology. ISSN 0271-9142. 40(8). doi: 10.1007/s10875-020-00834-2. Full text in Research Archive Show summary

  Puumala hantavirus (PUUV) hemorrhagic fever with renal syndrome (HFRS) is common in Northern Europe; this infection is usually self-limited and severe complications are uncommon. PUUV and other hantaviruses, however, can rarely cause encephalitis. The pathogenesis of these rare and severe events is unknown. In this study, we explored the possibility that genetic defects in innate anti-viral immunity, as analogous to Toll-like receptor 3 (TLR3) mutations seen in HSV-1 encephalitis, may explain PUUV encephalitis. We completed exome sequencing of seven adult patients with encephalitis or encephalomyelitis during acute PUUV infection. We found heterozygosity for the TLR3 p.L742F novel variant in two of the seven unrelated patients (29%, p = 0.0195). TLR3-deficient P2.1 fibrosarcoma cell line and SV40-immortalized fibroblasts (SV40-fibroblasts) from patient skin expressing mutant or wild-type TLR3 were tested functionally. The TLR3 p.L742F allele displayed low poly(I:C)-stimulated cytokine induction when expressed in P2.1 cells. SV40-fibroblasts from three healthy controls produced increasing levels of IFN-λ and IL-6 after 24 h of stimulation with increasing concentrations of poly(I:C), whereas the production of the cytokines was impaired in TLR3 L742F/WT patient SV40-fibroblasts. Heterozygous TLR3 mutation may underlie not only HSV-1 encephalitis but also PUUV hantavirus encephalitis. Such possibility should be further explored in encephalitis caused by these and other hantaviruses.

• Hautala, Timo; Chen, Jie; Tervonen, Laura; Partanen, Terhi; Winqvist, Satu & Lehtonen, Johanna [Show all 17 contributors for this article] (2020). Herpes simplex virus 2 encephalitis in a patient heterozygous for a TLR3 mutation. Neurology: Genetics. ISSN 2376-7839. 6(6). doi: 10.1212/NXG.0000000000000532. Full text in Research Archive
• Laitila, Jenni; Lehtonen, Johanna; Lehtokari, Vilma-Lotta; Sagath, Lydia; Wallgren-Pettersson, Carina & Grönholm, Mikaela [Show all 7 contributors for this article] (2019). A nebulin super-repeat panel reveals stronger actin binding toward the ends of the super-repeat region. Muscle and Nerve. ISSN 0148-639X. doi: 10.1002/mus.26350..

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• Sulonen, Anna-Maija; Lehtonen, Johanna; Kaustio, Meri; Edgren, Henrik; Almusa, Henrikki & Ellonen, Pekka [Show all 15 contributors for this article] (2023). Copy number variations from exome sequencing of Finnish inborn errors of immunity cohort.
• Lehtonen, Johanna & Hassinen, Antti (2023). FIMM High Content Imaging and Analysis Unit Phenotyping Rare Neurological Disease Variants Using High-Content Imaging.
• Lehtonen, Johanna (2022). A summary of the 20th Biennial meeting of the European Society for Immunodeficiencies.
• Lehtonen, Johanna & Batlle-Masó, Laura (2022). Genetic studies in autoimmune lymphoproliferative syndrome pediatric patients.
• Lehtonen, Johanna; Hakonen, Anna H; Hassinen, Antti; Sulonen, Anna-Maija; Almusa, Henrikki & Palomäki, Maarit [Show all 14 contributors for this article] (2022). CCDC88A variants underly malformations of cortical development, profound developmental delay, epilepsy, and immune dysfunction.
• Lehtonen, Johanna; Hakonen, Anna H; Hassinen, Antti; Sulonen, Anna-Maija; Almusa, Henrikki & Palomäki, Maarit [Show all 14 contributors for this article] (2022). CCDC88A variants underly malformations of cortical development, profound developmental delay, epilepsy, and immune dysfunction.
• Lehtonen, Johanna; Hakonen, Anna H; Hassinen, Antti; Sulonen, Anna-Maija; Almusa, Henrikki & Palomäki, Maarit [Show all 13 contributors for this article] (2022). Genome sequencing reveals CCDC88A variants underlying malformations of cortical development, profound developmental delay, epilepsy, and immune dysfunction.
• Lehtonen, Johanna; Sulonen, Anna-Maija; Almusa, Henrikki & Saarela, Janna Saija (2022). Gaining long-read information synthetically using linked reads.
• Lehtonen, Johanna; Almusa, Henrikki; Savarese, Marco & Saarela, Janna Saija (2020). Haplotype and variant phasing of large muscle genes using linked-read sequencing.
• Lehtonen, Johanna; Lehtokari, Vilma-Lotta; Almusa, Henrikki; Sulonen, Anna-Maija; Saarela, Janna Saija & Wallgren-Pettersson, Carina [Show all 7 contributors for this article] (2019). Linked-read whole genome sequencing in patients with congenital myopathy.
• Lehtonen, Johanna; Khattab, Ayman; Laitila, Jenni; Grönholm, Mikaela; Wallgren-Pettersson, Carina & Lehtokari, Vilma-Lotta [Show all 7 contributors for this article] (2019). The microscale thermophoresis method for the analysis of nebulin-tropomyosin interaction.

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