De novo pathogenic DHX30 variants in two cases

Abstract

De novo pathogenic DHX30 variants in two casesDExH-Box Helicase 30 (DHX30) (NM_138615.3) mutations cause autosomal dominant neurodevelopmental disorder with severe motor impairment and absent language (OMIM #617804). At least 16 heterozygous pathogenic variants in DHX30 have been reported so far. [1][2][3] Here, we report two unrelated patients (Figure 1) with de novo missense DHX30 variants detected by whole exome sequencing and subsequent Sanger sequencing, as reported previously. 4 This study was approved by the Institutional Review Board of Yokohama City University School of Medicine. The detected variants are: c.2210C > T, p.Ser737Phe in Patient 1, which has been previously reported, 2,3 and c.2345G > A, p.Arg782Gln in Patient 2, whichwas novel but has since been described. 3 Both variants reduce ATPase activity, while p.Ser737Phe also impairs RNA helicase activity. 3 Both patients showed microcephaly, profound developmental delay, hypotonia, speech impairment, no independent walking, autistic behavior, stereotypic movements, scoliosis, cerebral atrophy, dilated ventricles, and delayed myelination, which is similar to DHX30-related disease. [1][2][3] Patient 1 (a 19-year-old Brazilian female) was born at term to non-consanguineous parents with unremarkable prenatal and family histories. She had a birth weight of 3045 g (À0.78 SD), length of 47 cm (À1.51 SD), and head circumference of 34 cm (À0.51 SD). She exhibited respiratory distress soon after birth and was intubated for 3 days. She sat at 3.