Clinical and genetic analysis of a novel CHD4 gene variant in a Chinese patient with Sifrim-Hitz-Weiss syndrome / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To explore the genotype-phenotype correlation of a case with Sifrim-Hitz-Weiss syndrome (SIHIWES) caused by a novel CHD4 gene variant.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the patient and her parents. Whole-exome sequencing (WES) was carried out for the patient.Suspected variant was verified by Sanger sequencing.@*RESULTS@#The proband, a 2-year-old Chinese girl, presented with global developmental delay, intellectual disability, distinctive facial features and multiple congenital anomalies. Her prenatal manifestations included increased nuchal thickness, cranial and facial anomalies, and decreased fetal movement. WES has identified a novel variant in the CHD4 gene, namely NM_001273c.2989C>G (p.Leu997Val) (GRCh37/hg19).Comparison of her phenotype with previously reported SIHIWES cases suggested that our patient's prenatal presentations were unreported before, with novel features including funduscopic anomaly, facial dysmorphisms such as asymmetrical ears, drooping eyelid, long philtrum and downturned mouth.@*CONCLUSION@#Above findings have expanded the mutational spectrum of the CHD4 gene and revealed novel phenotypes in Chinese patients with SIHIWES.