scholarly journals A case of autosomal recessive hypercholesterolemia with a novel mutation in the LDLRAP1 gene

2021 ◽  
Vol 30 (4) ◽  
pp. 201-204
Author(s):  
Parisa Nikasa ◽  
Bahareh Rabbani ◽  
Mohammad Saeid Hejazi ◽  
Ata Firouzi ◽  
Hossein Baharvand ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Novel Mutation ◽  
Autosomal Recessive Hypercholesterolemia ◽  
I Gene

scholarly journals A case of autosomal recessive hypercholesterolemia with a novel mutation in the LDLRAP1 gene

2021 ◽  
Author(s):  
Parisa Nikasa ◽  
Bahareh Rabbani ◽  
Mohammad Saeid Hejazi ◽  
Ata Firouzi ◽  
Hossein Baharvand ◽  
...  
Keyword(s):  
Amino Acid ◽  
Aortic Valve ◽  
Coronary Arteries ◽  
Nonsense Mutation ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Artery Bypass ◽  
Her Family ◽  
Autosomal Recessive Hypercholesterolemia ◽  
Stenotic Lesions

Abstract Background: Autosomal recessive hypercholesterolemia (ARH) is a rare monogenic disorder resulting from mutations of the LDLRAP1 gene, which leads to elevated LDL-C levels. Here, using whole exome sequencing (WES), we describe a 22-year-old Iranian female who carries a novel nonsense mutation in LDLRAP1. Methods: Genetic investigations were performed for the patient and her family. She showed LDL-C level of 720 mg/dL since the age of 11 years. At the age of 13 years old, aortic valve repair surgery was performed due to severe aortic valve stenosis (AVS). At the age of 17, along with prescription of rosuvastatin plus ezetimibe, coronary angiography displayed the presence of serious stenotic lesions of the coronary arteries and also aortic valve, making the patient eligible for coronary artery bypass grafting (CABG) and aortic valve replacement (AVR). Results: Genetic analysis showed the presence of a previously unreported homozygous LDLRAP1 gene variant, c.649G>T, generating a nonsense mutation at amino acid 217, shortening the ARH protein from 308 to 217 amino acid, which removes AP-2 binding domain of ARH, as an important part in LDL uptake.Conclusion: During a 10-year treatment, we observed a 74% reduction in LDL-C level. Despite the treatment with maximal dose of rosuvastatin plus ezetimibe, the results of coronary angiography demonstrated severe supravalvular aortic stenosis (SVAS) resulted in significant stenotic lesions of the coronary arteries and aortic valve. This highlights the importance of WES in early diagnosis of ARH, and it is proposed to prevent or at least delay the onset of the cardiovascular events.

Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 692-694 ◽  
Author(s):  
Daniel F. Wallace ◽  
Palle Pedersen ◽  
Jeannette L. Dixon ◽  
Peter Stephenson ◽  
Jeffrey W. Searle ◽  
...  
Keyword(s):  
Iron Transport ◽  
Autosomal Recessive ◽  
Iron Homeostasis ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Hfe Gene ◽  
Excess Iron ◽  
Chromosome 1Q ◽  
Australian Family ◽  
Autosomal Recessive Pattern

Abstract Hemochromatosis is a common disorder characterized by excess iron absorption and accumulation of iron in tissues. Usually hemochromatosis is inherited in an autosomal recessive pattern and is caused by mutations in the HFE gene. Less common non-HFE–related forms of hemochromatosis have been reported and are caused by mutations in the transferrin receptor 2 gene and in a gene localized to chromosome 1q. Autosomal dominant forms of hemochromatosis have also been described. Recently, 2 mutations in theferroportin1 gene, which encodes the iron transport protein ferroportin1, have been implicated in families with autosomal dominant hemochromatosis from the Netherlands and Italy. We report the finding of a novel mutation (V162del) in ferroportin1 in an Australian family with autosomal dominant hemochromatosis. We propose that this mutation disrupts the function of the ferroportin1 protein, leading to impaired iron homeostasis and iron overload.

A novel mutation in thePLCD1gene, which leads to an aberrant splicing event, underlies autosomal recessive leuconychia

2012 ◽  
Vol 167 (4) ◽  
pp. 946-949 ◽  
Author(s):  
M. Farooq ◽  
M. Kurban ◽  
O. Abbas ◽  
O. Obeidat ◽  
H. Fujikawa ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Novel Mutation ◽  
Aberrant Splicing

scholarly journals A New Locus for Autosomal Recessive Hypercholesterolemia Maps to Human Chromosome 15q25-q26

2000 ◽  
Vol 66 (2) ◽  
pp. 453-460 ◽  
Author(s):  
Milco Ciccarese ◽  
Adolfo Pacifico ◽  
Giancarlo Tonolo ◽  
Paolo Pintus ◽  
Andrej Nikoshkov ◽  
...  
Keyword(s):  
Human Chromosome ◽  
Autosomal Recessive ◽  
Autosomal Recessive Hypercholesterolemia

Unusual presentation of a severe autosomal recessive anhydrotic ectodermal dysplasia with a novel mutation in theEDARgene

2008 ◽  
Vol 146A (20) ◽  
pp. 2657-2662 ◽  
Author(s):  
Hala Mégarbané ◽  
Céline Cluzeau ◽  
Christine Bodemer ◽  
Sylvie Fraïtag ◽  
Myrna Chababi-Atallah ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Ectodermal Dysplasia ◽  
Novel Mutation ◽  
Unusual Presentation

Abstract 1921: Clinical Impact of Heterozygous Carrier of Autosomal Recessive Hypercholesterolemia on Asymptomatic Hyperlipidemic Patients: Evidence From Familial Gene Analysis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hayato Tada ◽  
Masa-aki Kawashiri ◽  
Tohru Noguchi ◽  
Chiaki Nakanishi ◽  
Masayuki Tsuchida ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Genetic Defect ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Adaptor Protein ◽  
Receptor Internalization ◽  
Single Mutation ◽  
Heterozygous Carrier ◽  
Autosomal Recessive Hypercholesterolemia

Autosomal recessive hypercholesterolemia (ARH) is an extremely rare genetic defect, and is recognized only around 50 cases in all over the world. The genetic cause of ARH is mutation in an adaptor protein involved in low-density lipoprotein (LDL) receptor internalization, which results in marked elevation of serum LDL cholesterol (LDL-C) and premature atherosclerosis. Therefore, few data exist regarding the clinical significance about the heterozygous carrier of ARH. We recently identified the second ARH patient (Ins C 599 ) in Japan and his some relatives who have the same single mutation (heterozygous). We identified 11 heterozygous ARH carriers (male=5, mean age=48.2) and 7 non-carriers (male=3, mean age=53.3) in the same family. In addition, we screened the same mutations in unrelated consecutive 500 hyperlipidemic patients (male=32, mean age=49.4) with mean LDL-C of 225.2±6.1mg/dl using PCR to determine its frequency and examined their clinical features. We identified an unrelated heterozygous ARH carrier and a non-carrier in the same family among unrelated to the original family. Serum LDL-C levels of heterozygous ARH carriers (mean=153.8±35.8mg/dl) were significantly higher than those of non-carriers (mean=108.2±41.4mg/dl, p<0.05). Serum triglyceride (151.9±110.7mg/dl vs 140.4±48.8mg/dl) and high-density lipoprotein cholesterol (57.4±11.0mg/dl vs 54.0±11.9mg/dl) levels were not different between them. Interestingly, heterozygous ARH carriers didn’t show any xanthomas including Achilles tendon (6.4±1.1mm vs 5.7±1.1mm) in contrast to FH, which is frequently associated with typical xanthoma. These results demonstrate that heterozygous ARH (Ins C 599 ) carriers show higher LDL-C levels compared with non-carrier family member without tendon xanthomas observed in FH. We suggest that heterozygous ARH (Ins C 599 ) carrier may explain a part of primary hypercholesterolemia.

A novel mutation in the GTP cyclohydrolase I gene associated with a broad range of clinical presentations in a family with autosomal dominant dopa-responsive dystonia

1999 ◽  
Vol 6 (5) ◽  
pp. 605-608 ◽  
Author(s):  
Elena D. Markova ◽  
Pyotr A. Slominsky ◽  
Sergei N. Illarioshkin ◽  
Natalya I. Miklina ◽  
Svetlana N. Popova ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Gtp Cyclohydrolase I ◽  
Gtp Cyclohydrolase ◽  
Clinical Presentations ◽  
I Gene
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