Diagnosing CAH-X syndrome by long-read sequencing and identifying a novel genotype

BACKGROUND: To conduct long-read sequencing (LRS) testing for molecular diagnosis of CAH-X syndrome. This study collected clinical data and evaluated the phenotypes of Ehlers-Danlos syndrome (EDS) in 20 cases of 21-hydroxylase deficiency (21-OHD) children and performed genetic diagnosis for CAH-X syndrome by LRS. RESULTS: Two of the 20 cases of pediatric patients with 21-OHD were ultimately diagnosed with CAH-X syndrome. Both patients were presented with concurrent phenotypes of EDS and 21-OHD, 1 of whom exhibited a novel CAH-X genotype resulting from large gene conversion between the CYP21A2-TNXB gene (chr6:32039426–32044184) and CYP21A1P-TNXA pseudogene, whereas the other patient carried a TNXA/TNXB_CH-1 chimeric gene. CONCLUSIONS: This study identified a novel CAH-X genotype resulting from a large gene conversion and indicates that LRS may be a more reliable method for genetic diagnosis of CAH-X syndrome.