Akademik Veri Yönetim Sistemi
European Human Genetics Conference, Milan, İtalya, 24 - 27 Mayıs 2025, ss.260, (Özet Bildiri)
Background: Borjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability disorder caused by pathogenic variants in the PHF6 gene. The clinical spectrum includes intellectual disability/developmental delay (ID/DD), truncal obesity, hypogonadism, distinctive facial dysmorphism and features resembling Coffin-Siris syndrome. Although BFLS predominantly affects males, heterozygous females may also display clinical manifestations due to skewed X-chromosome inactivation. Here, we present a heterozygous female patient diagnosed with BFLS, illustrating the clinical and molecular findings associated with this rare disorder.
Material and methods: Whole-exome sequencing (WES) was initially performed, followed by Sanger sequencing for family segregation analysis. Chromosome analysis was performed to evaluate chromosomal abnormalities.
Results: In a 6.5-year-old female patient, clinical findings included ID/DD, horseshoe kidney, and features resembling Coffin-Siris syndrome, including hypertrichosis, bilateral hypoplastic fifth fingers, and prominent sandal gap. Chromosome analysis showed a normal 46,XX karyotype. WES analysis revealed a novel de-novo heterozygous variant, c.740C>G,p.(Ser247Cys), in exon 8 of the PHF6 gene (NM_001015877.2) classified as a variant of uncertain significance(PM2,PM6,PP3).
Conclusion: In this case, we present a female patient with a heterozygous variant in an X-linked gene, highlighting the complexity of diagnosing X-linked disorders. While X-linked recessive diseases typically affect males, females can also be impacted due to mechanisms such as skewed X-chromosome inactivation. This case emphasizes the importance of considering these mechanisms in variant analysis, particularly in female patients who may exhibit atypical phenotypes. Further studies are needed to clarify the pathogenicity of this variant and its contribution to the patient's phenotype, thereby advancing our understanding of the genetic and clinical spectrum of BFLS.