To the editor: Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is generally diagnosed on the basis of clinical and biochemical findings. However, SERPING1 gene genotyping is required in certain special situations [1], while an accurate detection of the causative variant is essential for a successful prenatal or preimplantation diagnosis of C1-INH-HAE [2] as well as for a gene therapy to be considered [3]. Nevertheless, in 9.2%(from 3.8 to 17.9%) of C1-INH-HAE patients, the causal SERPING1 gene variant remains unidentified by the use of current genetic testing approaches, which provide information restricted to the exons and exon-intron boundaries [4]. The increasing use of next-generation sequencing (NGS) targeting full genomic gene sequence has definitely changed the study of hereditary diseases and has raised awareness of the relevance of deep intronic variations (located more than 100 base pairs away from exon-intron junctions). Until 2017, 185 deep intronic variants across 77 different diseaseassociated genes had been reported [5]. Using a custom NGS platform targeting the entire SERPING1 gene [6], we recently examined 14 unrelated C1-INH-HAE patients in whom conventional genotyping had failed to identify a causative variant in the coding region. In two of them, Greek in origin, we discovered a deep intronic variant (c.-22-155 G> T) in the first intron of SERPING1 gene [7] which was classified as pathogenic, according to ACMG-AMP 2015 guidelines [8]. Concomitantly, Hujová et al.[9] described in a Czech family another deep intronic variant (c. 1029+ 384 A> G) located in the intron 6 of the SERPING1 gene, and provided strong evidence for its pathogenicity. Here, we report a new C1-INH-HAE case of Hungarian origin in the family of which the c. 1029+ 384 A> G variant was detected by our custom NGS panel and was found segregated with the disease (Fig. 1). A 43-year-old female patient (III. 3) has been followed up at the Hungarian Angioedema Reference Center since her age of 3 years, when the diagnosis of C1-INH-HAE type I was established. Her grandfather (I. 2) had angioedema symptoms but he committed suicide at the age of 50; her mother (II. 5) suffocated of laryngeal edema at the age of 23 in the yard of the hospital. Family screening was performed by complement testing among all available first-degree blood relatives. Two symptomatic (II. 1 and II. 3) and an asymptomatic (III. 1) members of the family were newly diagnosed with hereditary C1-INH deficiency type I. All of them are followed up regularly (at least once a year) at our Center. HAE symptoms of patient II. 1 were mild (six attacks during a 22-year observational period). He has received acute treatment with plasmaderived C1-INH during HAE attacks. Patients II. 3, III. 1, and III. 2 were ranked in severe group as they have experienced in average more than 12 HAE attacks per year. In these cases, longterm prophylaxis was introduced. Demographics, clinical data, results of complement testing, and types of treatments are presented in Supplementary Table 1. Comparing the SERPING1 gene genotype of the patients of our Hungarian family with those of the Czech family reported by Hujová et al.[9], we found that, beyond the pathogenic c. 1029+ 384 A> G variant, they also share the c.-21 T (rs28362944), c. 1029+ 84 G (rs118132731) c. 1030-20 G (rs2511988) haplotype. This finding indicates that the two families might be related to and originated from a common ancestor. Taken together with our previous results [7], the above case escalates up to 20% the percentage of pathogenic deep