Screening for Mutations in ABCC8 and KCNJ11 Genes in  Saudi Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI) Patients

Adi, Ahmad; Abbas, Bassam Bin; Hamed, Mohamed Al; Tassan, Nada Al; Bakheet, Dana

doi:10.3390/genes6020206

Cited by 2 publications

(2 citation statements)

References 29 publications

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“…Until diazoxide is proven to be safe, we do not recommend diazoxide as a treatment for pulmonary hypertension. While SUR1-dependent K ATP activation is an intriguing potential basis for pulmonary hypertension therapy, 32 ultimately, K ATP channel activators with less pulmonary toxicity may prove useful for pulmonary hypertension treatment. 33…”

Section: Discussionmentioning

confidence: 99%

Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension

Bohnen

Zhu

et al. 2018

Circ: Genomic and Precision Medicine

103

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Background: In pulmonary arterial hypertension (PAH), pathological changes in pulmonary arterioles progressively raise pulmonary artery pressure and increase pulmonary vascular resistance, leading to right heart failure and high mortality rates. Recently, the first potassium channelopathy in PAH, due to mutations in KCNK3, was identified as a genetic cause and pharmacological target. Methods: Exome sequencing was performed to identify novel genes in a cohort of 99 pediatric and 134 adult onset group I pulmonary arterial hypertension patients. Novel rare variants in the gene identified were independently identified in a cohort of 680 adult onset patients. Variants were expressed in COS cells and function assessed by patch-clamp and rubidium flux analysis. Results: We identified a de novo novel heterozygous predicted deleterious missense variant c.G2873A (p.R958H) in ABCC8 (ATP-binding cassette, subfamily C, member 8) in a child with idiopathic PAH. We then evaluated all individuals in the original and a second cohort for rare or novel variants in ABCC8 and identified 11 additional heterozygous predicted damaging ABCC8 variants. ABCC8 encodes sulfonylurea receptor 1 (SUR1), a regulatory subunit of the ATP-sensitive potassium channel (KATP). We observed loss of KATP function for all ABCC8 variants evaluated, and pharmacological rescue of all channel currents in vitro by the SUR1 activator, diazoxide. Conclusions: Novel and rare missense variants in ABCC8 are associated with pulmonary arterial hypertension. Identified ABCC8 mutations decreased KATP channel function, which was pharmacologically recovered.

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Section: Discussionmentioning

confidence: 99%

Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension

Bohnen

Zhu

et al. 2018

Circ: Genomic and Precision Medicine

103

View full text Add to dashboard Cite

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“…In Arabian descent populations, four studies have been performed; one in Tunisia that showed high prevalence of c.1227-1228dup [ 30 ] , the second in Morocco that introduced three variants (c.494A>G, c.1145G>A, and c.1185_1186dup) [ 31 ] , the third in Saudi Arabia that revealed the presence of V22M, Y165C, H324Q, and G382D variants [ 32 ] , and the last in Egypt that found a significant association between G396D and Y179C mutations and colorectal carcinogenicity [ 33 ] . These results contradict with those obtained from a study involved 360 Arabic patients [ 34 ] .…”

Section: Discussionmentioning

confidence: 99%

Association of a New Germline Variant in the MUTYH DNA Glycosylase Gene with Colorectal Adenoma Transformation into Malignancy

Mahasneh

Al-Shaheri

Banihani

2019

ibj

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Background: MUTYH DNA glycosylase germline mutations are linked to the recessive inheritance of multiple adenoma. Studies have revealed that germline mutations in this gene are ethnicity related. This study aimed to identify the germline mutations in MUTYH gene and determine their prevalence among Jordanian patients with colorectal adenoma. Methods:In this study, 150 colorectal adenoma patients and 150 cancer-free individuals with no previous history of polyps were recruited. Sanger DNA sequencing of the MUTYH gene (accession number NG_008189.1) was carried out using 3130xL Genetic Analyzer. Sequencing results were analyzed by ChromasPro, and mutational effects were predicted by online bioinformatics tools. Results:Two novel variants, g.87C>T and c.1264G>C, were identified. g.87C>T was also found in 60 (40%) patients and 10 (6.7%) controls. However, c.1264G>C was detected in 90 (60%) patients and 7 (4.7%) controls. Thus, a significant association was observed between these two variants and colorectal adenoma (p value for both variants was <0.0001). Moreover, the newly identified germline variant, c.1264G>C, was found to be significantly associated with colorectal adenoma transformation into malignancy (p < 0.0001). Conclusion:The data showed high prevalence of two germline mutations in MUTYH gene among Jordanians with colorectal adenoma, which may make them as potential early biomarkers for diagnosis of colorectal adenoma.

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Screening for Mutations in ABCC8 and KCNJ11 Genes in Saudi Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI) Patients

Cited by 2 publications

References 29 publications

Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension

Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension

Association of a New Germline Variant in the MUTYH DNA Glycosylase Gene with Colorectal Adenoma Transformation into Malignancy

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