Abstract
PURPOSE: The study aimed to explore the molecular defects underlying FXIII deficiency. MATERIALS AND METHODS: Sixteen unrelated cases were enrolled based on the indication of the urea clot solubility test and Factor XIII-A antigen levels. Cases were further subjected to targeted next-generation sequencing (custom gene panel: F7, F8, VWF, F9, F13A1, F13B). The pathogenic/likely pathogenic variants were validated by Sanger sequencing in the patients and family members. RESULTS: Mean age of referral to our center was 27.2 years (8 week-67 years). Consanguinity was found in only one of the 16 cases and 9 cases presented in infancy. The most common symptoms were skin bleeds (69%) and umbilical cord bleed (50%). The clot solubility test was positive in 12, inconclusive in 1, and normal in 3. Mean FXIII-A levels were 15.7 IU/dL (range 0.6 to 49.5 IU/dL). Pathogenic/likely pathogenic variants in F13A1 were found in 11 (69%). Nine cases (82%) were homozygous, and two were compound heterozygous. Total eleven variants were found of which four were missense (c.1226G>A; c.998C>T; c.631G>C; c.2134A>C); three deletion (c.521delG; c.742delA; c.1405_1408delCAAA); two nonsense (c.1112G>A; c.1127G>A) and two splice site (c.1909-1G>C; c.2045G>A). No probably pathogenic variant was found in the F13B. CONCLUSION: Inherited FXIII deficiency with bleeding is associated with genetic defects in predominantly the F13A1 gene. A variety of variants were seen in this cohort. A nonsense variant c.1127G>A found in three of our cases seems to be recurrent. This data will contribute to designing functional studies and antenatal testing in affected families. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12288-022-01579-1.