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Background: Pitt–Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder that results from variants of TCF4 gene. PTHS follows an autosomal dominant inheritance pattern and the underlying pathological mechanisms of this disease are still unclear. Methods: Whole-genome sequencing (WGS) was conducted to screen for potential pathogenic variant in a boy highly suspected of having a genetic disorder. PCR and Sanger sequencing were used to verify the effects of the variant. Serum TCF4 levels were measured by ELISA. Results: We present a 4-year and 3-month-old Chinese boy clinically and molecularly diagnosed with PTHS. The proband experienced global development delay, and the preliminary clinical diagnosis was cerebral palsy. WGS identified a de novo heterozygous variant: c.*1A > G in the 3'UTR of the TCF4 gene as a potential cause of his condition. The variant was verified to cause aberrant mRNA splicing by PCR and the aberrant splicing was confirmed by Sanger sequencing. Conclusion: The study identified and demonstrated the pathogenicity of a novel 3'UTR site TCF4 variant for the first time. This research enhances understanding of pathogenetic mechanisms of PTHS and aids genetic counseling and diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Our aim is to determine prevalence, severity, duration of otorhinolaryngologic symptoms related to coronavirus disease 2019 (COVID-19), and correlation between the test results obtained by oronasopharyngeal swab and the symptoms of these regions by evaluating differences in ear, nose, and throat (ENT) symptoms between laboratory-confirmed COVID-19 patients and clinically and computed tomography (CT)-diagnosed COVID-19 patients. Methods: The study enrolled patients with a positive polymerase chain reaction (PCR) test diagnosed with COVID-19 that grouped as PCR (+), and those with repeated negative PCR tests but COVID-19 Reporting and Data System (CO-RADS) chest CT findings with high (CO-RADS 5) or very high (CO-RADS 6) similarity to COVID-19 that grouped as PCR(-)/CT(+). Demographic features, general symptoms, and otorhinolaryngological symptoms and severity of disease were evaluated and compared. Results: The most common ENT symptoms in the PCR(+) group were loss of taste (n=77), loss of smell, and sore throat with respective frequencies of 34.5%, 31.8%, 26.0%, and in PCR(-) CT (+) group loss of taste, loss of smell, and sore throat with respective frequencies 24.6%, 21.1%, and 18.4%. ENT symptom rates were found higher in PCR (+) group (65.0%) according to PCR(-)/CT(+) group (49.1%) with statistically significant difference (p=0.008). Loss of smell rates were found higher in PCR (+) group according to PCR(-)/CT(+) group with statistically significant difference (p=0.037). Conclusion: Loss of smell and taste were most common ENT symptoms in laboratory-confirmed COVID-19 cases. The presence of COVID-19 should definitely be considered in patients presenting with sudden loss of smell or taste. In addition, loss of smell and otolaryngologic symptoms were more common in laboratory-confirmed COVID-19 according to clinically and computed tomograpy diagnosed COVID-19 cases. There can be a correlation between positive sample region and symptom region. Location of symptoms must be considered for decision of sampling location. [ABSTRACT FROM AUTHOR]