Analysis of clinical phenotype and genetic variant in a case of familial hemophagocytic lymphohistiocytosis typeⅢ
10.3760/cma.j.cn511374-20210202-00107
- VernacularTitle:一个Ⅲ型家族性噬血细胞组织细胞增生症家系的临床及基因变异分析
- Author:
Yue WANG
1
;
Qiang LUO
;
Peichao TIAN
;
Yufeng LIU
;
Huaili WANG
Author Information
1. 郑州大学第一附属医院儿科，郑州 450052
- Keywords:
Type 3 familial hemophagocytic lymphohistiocytosis;
UNC13 D gene;
Intronic variant;
Splicing variant
- From:
Chinese Journal of Medical Genetics
2022;39(6):616-620
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic basis for a newborn with familial hemophagocytic lymphohistiocytosis type 3 (FHL3).Methods:Clinical and laboratory data of the newborn and his family members were reviewed. Whole exome sequencing (including and flanking intronic regions) was carried out. Candidate variants were verified by Sanger sequencing. Wild type and mutant minigene vectors containing exon 23, intron 23 and exon 24 of the UNC13D gene were constructed and transfected into HEK293T cells by lipofectamine reagent. Reverse transcription PCR was carried out to verify the splicing of the minigenes. Results:Pedigree analysis and clinical examinations indicated that the child has autosomal recessive FHL3. DNA sequencing revealed that he has harbored c. 118-308 (IVS1)C>T and c. 2298+ 1 (IVS23)G>A variants of the UNC13D gene, which were respectively inherited from his father and mother, which constituted compound heterozygosity and were both predicted to be pathogenic. Minigene experiment confirmed that the c. 2298+ 1(IVS23)G>A variant has resulted skipping of exon 23 (-207nt) resulting in a truncated protein. Conclusion:The c. 118-308(IVS1)C>T and c. 2298+ 1(IVS23)G>A compound heterozygous variants of the UNC13D gene probably underlay the FHL3 in this child, which has resulted in low expression as well as abnormal splicing of UNC13D mRNA.
