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  1. Article ; Online: Evolution of clinically isolated syndrome to pediatric-onset multiple sclerosis and a review of the literature.

    Solmaz, İsmail / Öncel, İbrahim

    Turkish journal of medical sciences

    2022  Volume 52, Issue 4, Page(s) 1281–1287

    Abstract: Background: Clinically isolated syndrome (CIS) may be the first presentation of pediatric onset multiple sclerosis (POMS). We retrospectively evaluated the clinical and laboratory data of pediatric CIS (pCIS) patients who were diagnosed with POMS upon ... ...

    Abstract Background: Clinically isolated syndrome (CIS) may be the first presentation of pediatric onset multiple sclerosis (POMS). We retrospectively evaluated the clinical and laboratory data of pediatric CIS (pCIS) patients who were diagnosed with POMS upon followup for any predictive variables. We also reviewed the literature concerning the management of pCIS.
    Methods: This single-center study involved patients who had pCIS in childhood that converted to POMS during followup between 2011 and 2021. Sixteen patients were included in the study. The data were evaluated retrospectively and analyzed with descriptive statistics.
    Results: The majority of the pCIS patients were female (F/M: 10/6, 62/38%), and the first pCIS attack was at 13.3 ± 2.6 years old (mean ± SD). Mean follow-up was 3.1 ± 1.4 years; 6 of the patients relapsed within 1 year and 6 within 2 years. The time from the first pCIS attacks of the patients to the diagnosis of POMS was 15.75 ± 11.07 months. The annualized relapse rate (ARR) was 0.9 ± 0.7. The majority (68%) of the patients had a monosymptomatic onset, optic neuritis (ON) being the most common initial presentation (44%). Cerebrospinal fluid (CSF) oligoclonal bands (OCBs) were found in 9/12 (75%) and the immunoglobulin G index (IgG index) was elevated in 5/11 (45%). An autoimmune disorder was reported in the 1st or 2nd degree relatives of 6 patients: four (25%) MS, one ulcerative colitis, and one Hashimoto's thyroiditis. Our pCIS patients did not receive any disease-modifying treatment (DMT) for their first attack. When the diagnosis changed to POMS, most (68%) were started on interferons. The Expanded Disability Status Scale (EDSS) increased in one patient during follow-up (EDSS: 3) while in the others it was 0 at the last visit. The literature is reviewed in order to compare results for suggestions regarding the management of pCIS.
    Discussion: The presence of OCBs in the initial episode, MS in the family, and monosymptomatic onset may increase the possibility of developing POMS. Whether DMTs given at the pCIS stage are effective in preventing relapses and disability needs to be evaluated in longitudinal follow-up of large cohorts.
    MeSH term(s) Humans ; Child ; Female ; Male ; Adolescent ; Multiple Sclerosis/diagnosis ; Multiple Sclerosis/epidemiology ; Retrospective Studies ; Demyelinating Diseases ; Recurrence ; Disease Progression
    Language English
    Publishing date 2022-08-10
    Publishing country Turkey
    Document type Review ; Journal Article
    ZDB-ID 1183461-4
    ISSN 1303-6165 ; 1300-0144
    ISSN (online) 1303-6165
    ISSN 1300-0144
    DOI 10.55730/1300-0144.5434
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Rhombencephalitis and longitudinal extensive myelitis associated with dinutuximab use in high-risk neuroblastoma.

    Atak, Fırat / Aydın, Güzide Burça / Öncel, İbrahim / Öz, Sibel / Oğuz, Kader Karlı

    The Turkish journal of pediatrics

    2023  Volume 65, Issue 3, Page(s) 523–530

    Abstract: Background: Dinutuximab is a monoclonal antibody that targets the GD2 antigen used in the treatment of high-risk neuroblastoma. Dinutuximab-associated rhombencephalitis and myelitis is a rare, steroid-responsive, serious, but reversible pathology. To ... ...

    Abstract Background: Dinutuximab is a monoclonal antibody that targets the GD2 antigen used in the treatment of high-risk neuroblastoma. Dinutuximab-associated rhombencephalitis and myelitis is a rare, steroid-responsive, serious, but reversible pathology. To date, three transverse myelitis cases and one rhombencephalitis case due to dinutuximab have already been reported. Moreover, a recently published article identified five inflammatory CNS demyelination cases (four myelitis and one rhombencephalitis). We present a 5-year-old patient with rhombencephalitis and myelitis following dinutuximab-beta treatment.
    Case: A 5-year-old patient with a left-sided retroperitoneal mass infiltrating the left kidney and multiple lytic bone lesions was diagnosed with neuroblastoma with a percutaneous biopsy from the abdominal mass. Surgery was performed after a prominent treatment response was detected on the abdominal CT. Radiotherapy was applied to the abdomen. While she was still undergoing maintenance treatment with 13-cis retinoic acid, a metaiodobenzylguanidine (MIBG) scan detected new bone lesions, and brain MRG identified pachymeningeal involvement. A new chemotherapy regimen was started and decreased MIBG uptake was seen in all previous bone lesions. However, newly developed eighth rib metastasis was seen in the following MIBG scan. Autologous stem cell transplantation was done. Soon after, dinutuximab-beta, together with temozolomide and irinotecan, was initiated. Following the third cycle hypotension, somnolence, paraparesis, and unilateral fixed dilated pupil were developed. Afterward, hemiballismus-like irregular limb movements were observed. Work-up studies were unremarkable, except for hypodensity in the brain stem on the brain CT. MRI revealed T2 hyperintensity of the brainstem and spinal cord extending from the cervicomedullary junction to the T7 level. Moreover, incomplete contrast enhancement and facilitated diffusion were observed. Imaging findings suggested demyelination. Steroids and intravenous immune globulin (IVIG) treatment were initiated. Both imaging abnormalities and clinical symptoms resolved partially at one month and disappeared at six months.
    Conclusions: Awareness of the radiological findings of dinutuximab toxicity will lead to prompt diagnosis and treatment.
    MeSH term(s) Female ; Humans ; Child, Preschool ; 3-Iodobenzylguanidine/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Antibodies, Monoclonal/adverse effects ; Neuroblastoma/diagnostic imaging ; Neuroblastoma/drug therapy ; Myelitis/drug therapy ; Demyelinating Diseases/drug therapy
    Chemical Substances dinutuximab (7SQY4ZUD30) ; 3-Iodobenzylguanidine (35MRW7B4AD) ; Antibodies, Monoclonal
    Language English
    Publishing date 2023-01-31
    Publishing country Turkey
    Document type Case Reports
    ZDB-ID 123487-0
    ISSN 2791-6421 ; 0041-4301
    ISSN (online) 2791-6421
    ISSN 0041-4301
    DOI 10.24953/turkjped.2022.598
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Interplay between carotid artery dissection and thrombophilia leading to ischaemic stroke after minor head trauma in an adolescent: a case report.

    Hanalioglu, Damla / Oncel, Ibrahim / Hanalioglu, Sahin / Cebeci, Dilek / Kurt, Funda / Gunes, Altan / Gurkas, Esra

    Paediatrics and international child health

    2023  Volume 43, Issue 1-3, Page(s) 13–18

    Abstract: Stroke in children is more common than is often realised; there are numerous potential causes, including carotid artery injury resulting from minor head or neck trauma, as well as genetic conditions associated with thrombophilia. A 13-year-old boy ... ...

    Abstract Stroke in children is more common than is often realised; there are numerous potential causes, including carotid artery injury resulting from minor head or neck trauma, as well as genetic conditions associated with thrombophilia. A 13-year-old boy suffered an arterial ischaemic stroke (AIS) secondary to dissection of the left internal carotid artery (ICA) after he headed the ball during a game of football. He presented with generalised tonic-clonic seizure, loss of consciousness, right-sided hemiplegia and aphasia. Neuroradiological imaging showed left caudate, putaminal and posterior insular ischaemic infarct secondary to complete occlusion of the left ICA and accompanying partial left middle cerebral artery occlusion. He was treated with anticoagulant and anti-aggregant agents. Rarely, minor head trauma can result in internal carotid artery dissection, thrombus formation and arterial occlusion, leading to arterial ischaemic stroke. Prompt diagnosis and management are crucial to achieve a good neurological outcome.
    MeSH term(s) Male ; Child ; Humans ; Adolescent ; Brain Ischemia/complications ; Stroke/etiology ; Carotid Artery, Internal ; Magnetic Resonance Angiography ; Craniocerebral Trauma/complications ; Ischemic Stroke/complications ; Thrombophilia/complications
    Language English
    Publishing date 2023-12-15
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 2649065-1
    ISSN 2046-9055 ; 2046-9047
    ISSN (online) 2046-9055
    ISSN 2046-9047
    DOI 10.1080/20469047.2023.2269362
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Corrigendum to "Subacute sclerosing panencephalitis and immune thrombocytopenia: More than a coincidence?" [Med. Hypotheses 111 (2018) 70-72].

    Oncel, Ibrahim / Saltik, Sema / Anlar, Banu

    Medical hypotheses

    2020  Volume 138, Page(s) 109619

    Language English
    Publishing date 2020-02-20
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 193145-3
    ISSN 1532-2777 ; 0306-9877
    ISSN (online) 1532-2777
    ISSN 0306-9877
    DOI 10.1016/j.mehy.2020.109619
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The Outcome of COVID-19 in Pediatric-Onset Multiple Sclerosis Patients.

    Oncel, Ibrahim / Alici, Nurettin / Solmaz, Ismail / Oge, Dogan Dinc / Ozsurekci, Yasemin / Anlar, Banu

    Pediatric neurology

    2022  Volume 134, Page(s) 7–10

    Abstract: Background: The pathogenesis of multiple sclerosis (MS) involves immune-mediated mechanisms, and disease-modifying therapies (DMTs) administered in MS have immunomodulatory effects. The concern about MS patients' susceptibility to coronavirus disease ... ...

    Abstract Background: The pathogenesis of multiple sclerosis (MS) involves immune-mediated mechanisms, and disease-modifying therapies (DMTs) administered in MS have immunomodulatory effects. The concern about MS patients' susceptibility to coronavirus disease 2019 (COVID-19) has prompted several studies based on clinical observations and questionnaires. Information about COVID-19 in pediatric-onset multiple sclerosis (POMS) is scarce. The objective of this study was to collect information on the experience of POMS patients with COVID-19 during the pandemic.
    Methods: This cross-sectional study was conducted with POMS patients diagnosed at Hacettepe University Pediatric Neurology Department and under 23 years of age between October 1 and December 31, 2021. Those who experienced COVID-19 or had a history of contact and were found seropositive for COVID-19 were evaluated for the severity of COVID-19, disability, treatment status, and comorbidities.
    Results: Among the 101 POMS patients, 13 reported having had COVID-19 and five were exposed and seropositive but clinically asymptomatic. Of these 18 patients, 14 were ≤18 years of age at the time of the study. All 13 patients (72%) reported mild symptoms without hospitalization or respiratory support. Four of 18 had a neurological disability (Expanded Disability Status Scale [EDSS] scores ranging between 1 and 7.5), while the remaining had a score of 0. The outcome of COVID-19 was not affected by DMTs, neurological disabilities, and comorbidities.
    Conclusions: In this single-center POMS series, the small subgroup of patients who had contacted the SARS-CoV-2 virus or developed COVID-19 had reported no or mild symptoms. This may be partly related to the infrequent use of rituximab in this group. Our results corroborate those in adult-onset MS where no increased risk is reported for patients whose EDSS scores are <6 and who are not on B cell-depleting DMTs. Although less frequently than in adult MS, immunosuppressive DMTs may be needed in POMS; therefore, the importance of appropriate vaccination is to be underlined.
    MeSH term(s) Adult ; COVID-19/complications ; Child ; Cross-Sectional Studies ; Humans ; Multiple Sclerosis/complications ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/epidemiology ; Pandemics ; SARS-CoV-2
    Language English
    Publishing date 2022-06-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639164-3
    ISSN 1873-5150 ; 0887-8994
    ISSN (online) 1873-5150
    ISSN 0887-8994
    DOI 10.1016/j.pediatrneurol.2022.06.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Frequency of myelin oligodendrocyte glycoprotein antibodies in pediatric onset multiple sclerosis.

    Solmaz, Ismail / Doran, Tansu / Yousefi, Mohammadreza / Konuskan, Bahadır / Oncel, Ibrahim / Vural, Atay / Anlar, Banu

    Multiple sclerosis and related disorders

    2022  Volume 68, Page(s) 104097

    Abstract: Background: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are associated with acute demyelinating syndromes and only rarely detected in multiple sclerosis (MS). As MOG-Ab associated disease is common in childhood, we speculated young patients ... ...

    Abstract Background: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are associated with acute demyelinating syndromes and only rarely detected in multiple sclerosis (MS). As MOG-Ab associated disease is common in childhood, we speculated young patients might be more likely to produce MOG-Ab and investigated the frequency of MOG-Ab seropositivity in pediatric onset MS (POMS).
    Material and methods: Patients who experienced their first acute demyelinating event before age 18 years and were diagnosed with MS during follow-up were included in this single-center study. Patient data were retrieved from clinical records. Serum samples obtained and frozen at clinical visits were analyzed for MOG-Ab by a live cell-based assay (CBA) measuring delta mean fluorescence intensity (MFI) and MFI ratio. The control group consisted of patients referred to pediatric neurology for headache or vertigo and who had no neurological disorder (n = 48). Another control group consisted of patients with systemic inflammatory disorders systemic lupus erythematosus (n = 17) and juvenile idiopathic arthritis (n = 13) diagnosed in the rheumatology clinic.
    Results: The patient group (n = 122, F/M: 90/32, mean age 17.8 ± 2.6 years) were initially diagnosed as: MS, 62/122 (50.8%), clinically isolated syndrome, 43/122 (35.2%), radiologically isolated syndrome, 9/122 (7.3%), and acute disseminated encephalomyelitis 8/122 (6.5%). All received the final diagnosis of POMS. Serum was sampled 22.4 ± 29.2 (0-132) months after the first episode. None of the control groups had MOG-Ab positivity while 2/122 (1.6%) POMS cases had MOG-Abs, and a third patient had positive MFI and a MFI ratio slightly below the cut-off. These three patients' initial and final diagnoses were MS, their annualized relapsing rates (ARRs) were 0.4-0.6, and most recent Expanded Disability Status Scale was 0.
    Conclusion: Low titers of MOG-Ab can be detected in a small number of POMS patients at similar frequency with adult MS. Our POMS cases with MOG-Abs presented brainstem-cerebellar findings or seizures and had low ARR. Further series and longer follow-up will define whether these cases differ significantly from MOG-Ab negative POMS cases.
    Language English
    Publishing date 2022-08-08
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2645330-7
    ISSN 2211-0356 ; 2211-0348
    ISSN (online) 2211-0356
    ISSN 2211-0348
    DOI 10.1016/j.msard.2022.104097
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Measles.

    Oncel, Ibrahim / Anlar, Banu / Yalaz, Kalbiye

    The New England journal of medicine

    2019  Volume 381, Issue 20, Page(s) 1978

    MeSH term(s) Humans ; Measles
    Language English
    Publishing date 2019-11-11
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc1912468
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Clinical features and outcomes of opsoclonus myoclonus ataxia syndrome.

    Yıldırım, Miraç / Öncel, İbrahim / Bektaş, Ömer / Tanalı, Gizem / Şahin, Süleyman / Kutluk, Tezer / Teber, Serap / Anlar, Banu

    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society

    2022  Volume 41, Page(s) 19–26

    Abstract: Objectives and methods: Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare neuroinflammatory disorder. We aimed to retrospectively evaluate clinical and laboratory data and outcomes of 23 children diagnosed with OMAS in two children's hospitals ... ...

    Abstract Objectives and methods: Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare neuroinflammatory disorder. We aimed to retrospectively evaluate clinical and laboratory data and outcomes of 23 children diagnosed with OMAS in two children's hospitals between 2010 and 2021.
    Results: There were 14 boys and 9 girls aged 4-113 months, median 24 months. Ten (43.5%) children had paraneoplastic causes: neuroblastoma/ganglioneuroblastoma (n = 9), acute lymphoblastic leukemia (n = 1). Three children had a postinfectious cause (upper respiratory tract infection in 2, EBV infection in 1) and two had a history of vaccination (varicella in 1, hepatitis A and meningococcal in 1). No underlying factor was identified in 8 (34.8%) children. Speech disorders were more frequent in patients with neural tumors than in those without (p = 0.017). Intravenous immunoglobulin and steroids were effective as initial treatment in most children. Rituximab resulted in at least mild improvement in all 6 children with persistent or recurrent symptoms. Nine (39%) children experienced at least one relapse. Neurological sequelae were detected in 13 (57%) children. There was no significant correlation between clinical characteristics and outcome, except for higher risk of relapse in case of incomplete recovery after first attack (p = 0.001).
    Conclusions: Acute lymphoblastic leukemia, vaccines against hepatitis A and meningococci can be included among antecedent factors in OMAS. Among clinical symptoms, speech problems might point to the likelihood of an underlying neoplasm in OMAS. Intravenous immunoglobulin and steroids may be chosen for initial treatment while rituximab can increase the chance of recovery in case of persistent or recurrent symptoms. The presence of relapse was associated with poor outcome.
    MeSH term(s) Male ; Child ; Female ; Humans ; Opsoclonus-Myoclonus Syndrome/drug therapy ; Opsoclonus-Myoclonus Syndrome/etiology ; Rituximab/therapeutic use ; Immunoglobulins, Intravenous/therapeutic use ; Retrospective Studies ; Hepatitis A ; Ataxia ; Steroids/therapeutic use ; Recurrence ; Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Chemical Substances Rituximab (4F4X42SYQ6) ; Immunoglobulins, Intravenous ; Steroids
    Language English
    Publishing date 2022-09-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 1397146-3
    ISSN 1532-2130 ; 1090-3798
    ISSN (online) 1532-2130
    ISSN 1090-3798
    DOI 10.1016/j.ejpn.2022.09.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Options in the Treatment of Subacute Sclerosing Panencephalitis: Implications for Low Resource Areas.

    Samia, Pauline / Oyieke, Katherine / Tunje, Dorcas / Udwadia-Hegde, Anaita / Feemster, Kristen / Oncel, Ibrahim / Anlar, Banu

    Current treatment options in neurology

    2022  Volume 24, Issue 3, Page(s) 99–110

    Abstract: Purpose of the review: Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressive, and frequently fatal neurodegenerative disorder caused by measles virus. The risk of SSPE remains significant globally, with fluctuating incidence noted in ... ...

    Abstract Purpose of the review: Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressive, and frequently fatal neurodegenerative disorder caused by measles virus. The risk of SSPE remains significant globally, with fluctuating incidence noted in in tandem with measles vaccine uptake. This review aims to explore the current global status of SSPE, its treatment, and preventive measures.
    Recent findings: An increase in measles cases have been reported in various parts of the world for different reasons related to the regional context of the outbreak. With reduction in measles vaccine doses since the onset of the COVID-19 pandemic, the future risk of SSPE can only accelerate. In recent years, subsequent cases of SSPE have been reported in the period following documented measles outbreaks in different settings. Concomitantly, there have been efforts to evaluate the efficacy of immunomodulatory, antiviral, and anti-seizure therapies that could ameliorate the devastating effects of this disease. This review elucidates on these approaches and their limitations, reasons for poor vaccine coverage in low- and middle-income countries, as well as the possible solutions to the prevention of measles and eventual avoidance of SSPE.
    Summary: Prevention of measles virus infection with the resultant sequelae would be the most effective strategy for the management of SSPE. This approach would be particularly important in low resource setting that currently bears the double burden of widespread communicable diseases and malnutrition.
    Language English
    Publishing date 2022-03-19
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057342-X
    ISSN 1534-3138 ; 1092-8480
    ISSN (online) 1534-3138
    ISSN 1092-8480
    DOI 10.1007/s11940-022-00710-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Natural history of TRPV4-Related disorders: From skeletal dysplasia to neuromuscular phenotype.

    Ürel-Demir, Gizem / Şimşek-Kiper, Pelin Özlem / Öncel, İbrahim / Utine, Gülen Eda / Haliloğlu, Göknur / Boduroğlu, Koray

    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society

    2021  Volume 32, Page(s) 46–55

    Abstract: TRPV4-related disorders constitute a broad spectrum of clinical phenotypes including several genetic skeletal and neuromuscular disorders, in which clinical variability and somewhat overlapping features are present. These disorders have previously been ... ...

    Abstract TRPV4-related disorders constitute a broad spectrum of clinical phenotypes including several genetic skeletal and neuromuscular disorders, in which clinical variability and somewhat overlapping features are present. These disorders have previously been considered to be clinically distinct phenotypes before their molecular basis was discovered. However, with the identification of TRPV4 variants in the etiology, they are referred as TRPV4-related disorders (TRPV4-pathies), and are now mainly grouped into skeletal dysplasias and neuromuscular disorders. The skeletal dysplasia group includes metatropic dysplasia, parastremmatic dysplasia, spondyloepiphyseal dysplasia Maroteaux type, spondylometaphyseal dysplasia Kozlowski type, autosomal dominant brachyolmia, and familial digital arthropathy-brachydactyly, whereas the neuromuscular group includes congenital distal spinal muscular atrophy (SMA), scapuloperoneal SMA and Charcot-Marie-Tooth neuropathy type 2C with common manifestations of peripheral neuropathy, joint contractures, and respiratory system involvement. Apart from familial digital arthropathy-brachydactyly, skeletal dysplasia associated with TRPV4 pathogenic variants share some clinical features such as short stature with short trunk, spinal and pelvic changes with varying degrees of long bone involvement. Of note, there is considerable phenotypic overlap within and between both groups. Herein, we report on the clinical and molecular spectrum of 11 patients from six different families diagnosed with TRPV4-related disorders. This study yet represents the largest cohort of patients with TRPV4 variants from a single center in Turkey.
    MeSH term(s) Adolescent ; Bone Diseases, Developmental/genetics ; Bone Diseases, Developmental/pathology ; Child ; Child, Preschool ; Humans ; Infant ; Male ; Neuromuscular Diseases/genetics ; Neuromuscular Diseases/pathology ; Phenotype ; TRPV Cation Channels/genetics ; Turkey ; Young Adult
    Chemical Substances TRPV Cation Channels ; TRPV4 protein, human
    Language English
    Publishing date 2021-03-16
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 1397146-3
    ISSN 1532-2130 ; 1090-3798
    ISSN (online) 1532-2130
    ISSN 1090-3798
    DOI 10.1016/j.ejpn.2021.03.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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