Novel pathogenic CERKL variant in Iranian familial with inherited retinal dystrophies: genotype–phenotype correlation

Fu, Shangyi; Fu, Jiewen; Mobasher-Jannat, Abdolkarim; Jadidi, Khosrow; Li, Yumei; Chen, Rui; Imani, Saber; Cheng, Jingliang

doi:10.1007/s13205-023-03535-w

Cited by 1 publication

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“…A 10 µL Blood samples were collected, including from the proband and her 8 family members. DNA was extracted using proteinase K digestion and phenol/chloroform treatment [23,24]. Simultaneously, the whole blood proteins were lysed from the proband and her 5 family members for Western blotting.…”

Section: Sanger Verification and Co-segregation Analysismentioning

confidence: 99%

The ENG/VEGFα Pathway Is Likely Affected by a Nonsense Variant of Endoglin (ENG)/CD105, Causing Hereditary Hemorrhagic Telangiectasia Type 1 (HHT1) in a Chinese Family

Liu,

Fu,

Guo

et al. 2024

Genes

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Hereditary hemorrhagic telangiectasia (HHT), also called Rendu–Osler syndrome, is a group of rare genetic diseases characterized by autosomal dominance, multisystemic vascular dysplasia, and age-related penetrance. This includes arteriovenous malformations (AVMs) in the skin, brain, lung, liver, and mucous membranes. The correlations between the phenotype and genotype for HHT are not clear. An HHT Chinese pedigree was recruited. Whole exome sequencing (WES) analysis, Sanger verification, and co-segregation were conducted. Western blotting was performed for monitoring ENG/VEGFα signaling. As a result, a nonsense, heterozygous variant for ENG/CD105: c.G1169A:p. Trp390Ter of the proband with hereditary hemorrhagic telangiectasia type 1 (HHT1) was identified, which co-segregated with the disease in the M666 pedigree. Western blotting found that, compared with the normal levels associated with non-carrier family members, the ENG protein levels in the proband showed approximately a one-half decrease (47.4% decrease), while levels of the VEGFα protein, in the proband, showed approximately a one-quarter decrease (25.6% decrease), implying that ENG haploinsufficiency, displayed in the carrier of this variant, may affect VEGFα expression downregulation. Pearson and Spearman correlation analyses further supported TGFβ/ENG/VEGFα signaling, implying ENG regulation in the blood vessels. Thus, next-generation sequencing including WES should provide an accurate strategy for gene diagnosis, therapy, genetic counseling, and clinical management for rare genetic diseases including that in HHT1 patients.

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Section: Sanger Verification and Co-segregation Analysismentioning

confidence: 99%