Whole-exome sequencing identified a de novo variant of the AT-hook DNA-binding motif-containing protein 1 gene in a Chinese patient with Xia-Gibbs syndrome

AbstractObjective: This study investigated the genetic pathogenesis, clinical features, brain function, and neurobehavioral features of a Xia-Gibbs syndrome (XGS) pedigree.Methods:Candidate variants in the patient and his pedigree were indentified using whole-exome sequencing and Sanger sequencing.The patient's genetic and clinical features were analyzed referencing his pedigree and the literature.Brain dysfunction was evaluated using functional magnetic resonance imaging(fMRI).Resules:The patient carried a de novo variant c.3259dupT(p.Glu1087fs)in the AT-hook DNA-binging motif-containing protein 1 gene(AHDC1).The literature review indicated that the patient exhibited the typical features of XGS,including systemic developmental delay,hypotonia,intellectual disability,obstructive sleep apnea with snoring,and mild facial deformity.The patient demonstrated no behavioral abnormalities.The literature did not mention abnormal development of the fifth phalanx(single dermatoglyphic pattern),which was the patient's distinctive clinical feature.The fMRI diffusion tensor imaging sequences used the corpus callosum,brain stem,and frontosuboccipital tracts as the regions of interest (ROI) to track fiber bundles,which were sparse in all ROI.Resting-state fMRI was performed using the posterior cingulate cortex as the ROI to analyze its functional connectivity.Conclusion:This study determined that a XGS case was caused by a previously unreported c.3259dupT(p.Glu1087fs) mutation in the AHDC1 gene.Our findings expand the genotype and phenotype spectrum of XGS,which will guide genetic counseling and management of patients with this disease.Keywords:AHDC1 gene;whole-exome sequencing;brain functional magnetic resonance imaging;clinical phenotype;genotype