# Exploring factor XIII genetic diversity: a familial approach to inheritance and variation

## TL;DR

This study explores genetic mutations in Factor XIII deficiency within families, emphasizing the importance of combined approaches for accurate diagnosis and genetic counseling.

## Contribution

The study identifies specific mutations in Factor XIII deficiency families and highlights the value of integrating biochemical and clinical methods.

## Key findings

- Four families showed the IVS11 (+ 1) G > A mutation in homozygous patients.
- Two families exhibited the c.2045G > A mutation in their affected individuals.
- Consanguineous marriages were common in all studied families with bleeding disorders.

## Abstract

Plasma coagulation factor XIII (OMIM#134570 (F13A1) and 134580(F13B), synthesized in haematopoietic cells (FXIII-A) and hepatocytes (FXIII-B); stabilizes and protects fibrin clots against fibrinolytic breakdown, ensuring haemostasis. Inherited FXIII deficiency is a rare inherited autosomal recessive bleeding disorder affecting 1–3 million people globally and demonstrating strong consanguinity contributing to high incidence of cases in Pakistan. Patients manifesting severe illness are homozygotes or compound heterozygotes.

This study aims to estimate phenotypic traits, genetic alterations, and carrier rates in families with known genetic abnormalities in individuals with Factor XIII deficiency.

This cross-sectional study was approved by Advanced Studies Research Board and Ethical Review Committee of LUMHS, Jamshoro and conducted in concordance with Declaration of Helsinki 2000 in collaboration at the Biochemistry Department of LUMHS and Haematology Department, Baqai medical university, Karachi. Written informed consent obtained from all participants included in the study. Pedigree was constructed. Direct DNA sequencing performed via big dye terminator by using selective exon as per previously identified mutations in the patients of their families. FXIII confirmed with clot solubility testing and Elisa performed for Assay antigen detection for FXIII. Pathogenicity scoring done by using different software.

All the families had a history of consanguineous marriages and history of bleeding. From the six families, four families show same mutation in patient i.e. IVS11 (+ 1) G > A while two families showed c.2045G > A mutation in their homozygous patient.

The results of this study highlight how crucial it is to combine biochemical, clinical, and statistical approaches to increase the precision of diagnoses, improve patient treatment, and make genetic counselling easier for families who are at risk.