INTRODUCTION
The Wnt ligand secretion mediator is encoded by WLS, and biallelic variants in this gene have been associated with an ultra-rare syndrome known as Zaki syndrome (ZKS). This study presents the fourteenth documented case of ZKS globally and reviews the clinical and genetic information of previously identified ZKS patients.
METHODS
A 17-year-old female from Iran underwent whole-exome sequencing due to a range of phenotypic symptoms suggestive of a unique syndrome. Sanger sequencing was employed to validate the candidate variant and to investigate its segregation among family members.
RESULTS
The patient was found to be homozygous for NM_024911.7: c.1433A>G, p.(Tyr478Cys) located in exon 11 of WLS. She represents the fifth ZKS patient identified with this variant, indicating a possible mutational hotspot. Furthermore, our patient exhibited distinct clinical characteristics compared to previously reported cases, including hyperphagia, congenital blindness, clinodactyly, and early pubertal development. A comparison of all reported ZKS patients suggests that this syndrome displays a recognizable pattern of developmental delay, intellectual disability, postnatal microcephaly, facial dysmorphism, skeletal and ocular anomalies, and short stature. Nevertheless, challenges persist in diagnosing ZKS due to poorly defined genotype-phenotype correlations.
CONCLUSION
The clinical characteristics observed in our patient expand the phenotypic spectrum of ZKS. Additionally, the p.(Tyr478Cys) variant may represent a potential mutational hotspot within WLS.
Naeim Ehtesham, M. Mazaheri, Zahra Sadr et al.· European Journal of Medical...· 0 citations
Background: Granulomatosis with polyangiitis (GPA) is an autoimmune disorder that results from an interplay of genetic factors and environmental influences. We investigated the association between two polymorphisms in the VEGF gene, specifically rs2010963 and rs833061, and the likelihood of developing GPA. Methods: A case-control study involving 224 participants was conducted, comprising 104 individuals diagnosed with GPA and 120 control subjects. The high-resolution melting (HRM) technique was employed for genotyping these polymorphisms. Results: The findings revealed a significant difference in the distribution of the CC genotype and C allele for rs2010963 between the control and case groups (CC vs GG; OR: 2.687; 95% CI [1.185-6.264], P: 0.014; C vs G; OR: 1.628; 95% CI [1.097-2.421], P: 0.012). Moreover, patients with the GC + CC genotype exhibited elevated mean levels of creatinine, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), as well as a higher incidence of alveolar hemorrhage compared to those with the GG genotype. Concerning rs833061, no association with GPA risk was identified; however, correlations were noted with certain laboratory and clinical parameters, including PR3-ANCA levels, septal perforation, alveolar hemorrhage, renal involvement, and rapidly progressive glomerulonephritis (RPGN). Conclusion: The C allele of rs2010963 is linked to an increased risk of developing GPA and certain laboratory and clinical parameters, while the rs833061 polymorphism does not appear to be associated with GPA risk but is correlated with various laboratory and clinical indices.
Amirali Pourebrahimi, Mozhdeh Saghaei, Naeim Ehtesham et al.· Caspian Journal of Internal...· 0 citations
