Waardenburg syndrome (WS) is a clinically and genetically heterogeneous hereditary auditory pigmentary disorder characterized by congenital sensorineural hearing loss and iris discoloration. Many genes have been linked to WS, including PAX3, MITF, SNAI2, EDNRB, EDN3, and SOX10, and many additional genes have been associated with disorders with phenotypic overlap with WS. To screen all possible genes associated with WS and congenital deafness simultaneously, we performed diagnostic exome sequencing (DES) in a male patient with clinical features consistent with WS. Using DES, we identified a novel missense variant (c.220C>G; p.Arg74Gly) in exon 2 of the PAX3 gene in the patient. Further analysis by Sanger sequencing of the patient and his parents revealed a de novo occurrence of the variant. Our findings show that DES can be a useful tool for the identification of pathogenic gene variants in WS patients and for differentiation between WS and similar disorders. To the best of our knowledge, this is the first report of genetically confirmed WS in Korea.
Adult ; Amino Acid Sequence ; Asian Continental Ancestry Group/genetics ; Base Sequence ; DNA/chemistry/genetics/metabolism ; Exons ; Humans ; Male ; Mutation, Missense ; PAX3 Transcription Factor/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Republic of Korea ; Sequence Analysis, DNA ; Waardenburg Syndrome/*diagnosis/genetics

BACKGROUND/AIMS: We attempted to examine the relationship between abnormal findings on high-resolution manometry (HRM) and videofluoroscopic swallowing study (VFSS) of the pharynx and upper esophageal sphincter (UES), and to identify the risk factors for aspiration. METHODS: We performed VFSS and HRM on the same day in 36 ischemic stroke patients (mean age, 67.5 years) with dysphagia. Pressure (basal, median intra bolus, and nadir), relaxation time interval of the UES, and mesopharyngeal and hypopharyngeal contractility (as a contractile integral) were examined using HRM. The parameters of VFSS were vallecular residue, pyriform sinus residue, vallecular overflow, penetration, and aspiration. The association between the parameters of VFSS and HRM was analyzed by the Student's t test. RESULTS: Three (8.3%) and 4 (11.1%) stroke patients with dysphagia had pyriform sinus residue and vallecular sinus residue, respectively, and 5 (13.8%) patients showed aspiration. Mesopharyngeal and hypopharyngeal contractile integrals in patients with residue in the pyriform sinus were significantly lower than those in patients without residue in the pyriform sinus (P < 0.05). Relaxation time intervals in patients with aspiration were significantly shorter than those in patients without aspiration (P < 0.05), and multivariate regression analysis revealed a shorter relaxation time interval as the main risk factor for aspiration (OR, 0.03; 95% CI, 0.01–0.65; P < 0.05). CONCLUSIONS: Manometric measurements of the pharynx and UES were well correlated with abnormal findings in the VFSS, and a shorter relaxation time interval of the UES during deglutition is an important parameter for the development of aspiration.
Deglutition ; Deglutition Disorders* ; Esophageal Sphincter, Upper* ; Humans ; Manometry ; Pharynx ; Pyriform Sinus ; Relaxation* ; Risk Factors* ; Stroke*

Chromosomal loss in trisomy (trisomy rescue) to generate a disomic fetus can cause confined placental mosaicism and/or feto/placental mosaicism. After trisomy rescue event, there is a risk of fetal uniparental disomy (UPD). Noninvasive prenatal test (NIPT) reflects the genomic constitution of the placenta, not of the fetus itself. Feto-placental discrepancy can therefore cause false-positive (trisomy) NIPT results. These discordant NIPT results can serve as important clues to find UPD associated with confined placental mosaicism. We report a case with maternal UPD of chromosome 20, detected by NIPT of 1,000 high-risk pregnancies, carried out for detecting chromosomal abnormalities in Koreans.
Chromosome Aberrations ; Chromosomes, Human, Pair 20* ; Constitution and Bylaws ; Fetus ; Mosaicism ; Placenta ; Pregnancy, High-Risk* ; Trisomy ; Uniparental Disomy*