Helsmoortel-van der Aa syndrome in a Chinese pediatric patient due to ADNP nonsense mutation: A case report

Helsmoortel-van der Aa syndrome, also known as syndrome, is a condition that causes developmental delay, language impairment, autism spectrum, and variable extraneurologic features. It is caused by heterozygous mutations in the gene on chromosome 20q13. Most of the genetic causes of Helsmoortel-van der Aa syndrome have been reported are as nonsense or frameshift stop mutations in exon 5 of gene, while fewer truncating variants were discovered in exons 4 and the 5' end of exon 5. In our study, a 4-year-old female Chinese patient was reported with delayed psychomotor development, language impairment, ataxia, anxiety, aggressive behavior, and congenital heart defect. Trio whole exome sequencing and copy number variation sequencing were performed. A novel heterozygous pathogenic mutation c.568C > T (p.Gln190Ter) was identified in the gene of the proband. His unaffected parents did not have the variant. According to the American College of Medical Genetics (ACMG) guidelines, c.568C > T was classified as "pathogenic". Our report indicated that c.568C > T (p.Gln190Ter) in gene is the cause of abnormal development of the nervous system, congenital heart disease and strabismus, broadening the spectrum of gene mutations associated with Helsmoortel-van der Aa syndrome.