Am J Med Genet A. 2024 Dec 3:e63945. doi: 10.1002/ajmg.a.63945. Online ahead of print.
ABSTRACT
Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome characterized by pancytopenia, increased susceptibility to malignancies, and a spectrum of congenital anomalies. Here, we report on eight affected individuals from six unrelated families with a large Alu-mediated intragenic deletion encompassing exons 6-31 in the FANCA gene, identified as a founder mutation in the Turkish population through haplotype analysis. This deletion, mediated by Alu repeat sequences, underscores the role of repetitive elements in FA pathogenesis. Clinical data revealed variable phenotypic presentations among affected individuals, highlighting the challenge of establishing genotype-phenotype correlations even in the presence of identical FANCA pathogenic variants. We carried out an easy and effective PCR-based diagnostic test for detecting this mutation, enabling precise diagnosis and genetic counseling for affected individuals and their families. This study provides valuable insights into the molecular mechanisms underlying FA pathogenesis and offers a practical approach for genetic diagnosis in affected individuals, particularly those of Turkish descent.
PMID:39624858 | DOI:10.1002/ajmg.a.63945
