Low-density lipoprotein receptor gene mutation analysis and structure-function correlation in an Omani Arab family with familial hypercholesterolemia

Khalid Al-Rasadi; Khalid Al-Waili; Ward Al Muna Al-Zidi; Abdul Rahim Al-Abri; Ali T. Al-Hinai; Hilal Ali Al-Sabti; Sheikha Al-Tobi; Ibrahim Al-Zakwani; Fahad Al-Zadjali; Khamis Al-Hashmi; Yajnavalka Banerjee

doi:10.1177/0003319713510059

Low-density lipoprotein receptor gene mutation analysis and structure-function correlation in an Omani Arab family with familial hypercholesterolemia

Khalid Al-Rasadi, Khalid Al-Waili, Ward Al Muna Al-Zidi, Abdul Rahim Al-Abri, Ali T. Al-Hinai, Hilal Ali Al-Sabti, Sheikha Al-Tobi, Ibrahim Al-Zakwani, Fahad Al-Zadjali, Khamis Al-Hashmi, Yajnavalka Banerjee^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant disorder typified by elevated low-density lipoprotein cholesterol (LDL-C) levels caused by mutations in the LDL receptor (LDLR), apolipoprotein B (ApoB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Previously, we reported a novel mutation in the exon-3 of LDLR gene, observed in a 9-year-old Omani Arab female. Here, we investigated the mode of inheritance of this mutation and confirmed that FH in this family is due to mutation only in the LDLR and not PCSK9 and ApoB genes. Further, the effect of the mutation has been appraised in silico on the tertiary structure of LDLR. A model of the mutant LDLR has been constructed using the coordinates of the wild-type LDLR extracellular domain. Based on the model, we present a mechanistic justification behind the observed detrimental effect of the mutation on LDL-C levels.

Original language	English
Pages (from-to)	911-918
Number of pages	8
Journal	Angiology
Volume	65
Issue number	10
DOIs	https://doi.org/10.1177/0003319713510059
Publication status	Published - Nov 12 2014

Keywords

LDL receptor
Oman
Omani Arab
familial hypercholesterolemia
in silico

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1177/0003319713510059

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Al-Rasadi, K., Al-Waili, K., Al-Zidi, W. A. M., Al-Abri, A. R., Al-Hinai, A. T., Al-Sabti, H. A., Al-Tobi, S., Al-Zakwani, I., Al-Zadjali, F., Al-Hashmi, K., & Banerjee, Y. (2014). Low-density lipoprotein receptor gene mutation analysis and structure-function correlation in an Omani Arab family with familial hypercholesterolemia. Angiology, 65(10), 911-918. https://doi.org/10.1177/0003319713510059

Al-Rasadi, K , Al-Waili, K, Al-Zidi, WAM, Al-Abri, AR, Al-Hinai, AT, Al-Sabti, HA, Al-Tobi, S, Al-Zakwani, I, Al-Zadjali, F, Al-Hashmi, K & Banerjee, Y 2014, 'Low-density lipoprotein receptor gene mutation analysis and structure-function correlation in an Omani Arab family with familial hypercholesterolemia', Angiology, vol. 65, no. 10, pp. 911-918. https://doi.org/10.1177/0003319713510059

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title = "Low-density lipoprotein receptor gene mutation analysis and structure-function correlation in an Omani Arab family with familial hypercholesterolemia",

abstract = "Familial hypercholesterolemia (FH) is an autosomal dominant disorder typified by elevated low-density lipoprotein cholesterol (LDL-C) levels caused by mutations in the LDL receptor (LDLR), apolipoprotein B (ApoB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Previously, we reported a novel mutation in the exon-3 of LDLR gene, observed in a 9-year-old Omani Arab female. Here, we investigated the mode of inheritance of this mutation and confirmed that FH in this family is due to mutation only in the LDLR and not PCSK9 and ApoB genes. Further, the effect of the mutation has been appraised in silico on the tertiary structure of LDLR. A model of the mutant LDLR has been constructed using the coordinates of the wild-type LDLR extracellular domain. Based on the model, we present a mechanistic justification behind the observed detrimental effect of the mutation on LDL-C levels.",

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AU - Al-Rasadi, Khalid

AU - Al-Waili, Khalid

AU - Al-Zidi, Ward Al Muna

AU - Al-Abri, Abdul Rahim

AU - Al-Hinai, Ali T.

AU - Al-Sabti, Hilal Ali

AU - Al-Tobi, Sheikha

AU - Al-Zakwani, Ibrahim

AU - Al-Zadjali, Fahad

AU - Al-Hashmi, Khamis

AU - Banerjee, Yajnavalka

N1 - Publisher Copyright: © The Author(s) 2013.

PY - 2014/11/12

Y1 - 2014/11/12

N2 - Familial hypercholesterolemia (FH) is an autosomal dominant disorder typified by elevated low-density lipoprotein cholesterol (LDL-C) levels caused by mutations in the LDL receptor (LDLR), apolipoprotein B (ApoB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Previously, we reported a novel mutation in the exon-3 of LDLR gene, observed in a 9-year-old Omani Arab female. Here, we investigated the mode of inheritance of this mutation and confirmed that FH in this family is due to mutation only in the LDLR and not PCSK9 and ApoB genes. Further, the effect of the mutation has been appraised in silico on the tertiary structure of LDLR. A model of the mutant LDLR has been constructed using the coordinates of the wild-type LDLR extracellular domain. Based on the model, we present a mechanistic justification behind the observed detrimental effect of the mutation on LDL-C levels.

AB - Familial hypercholesterolemia (FH) is an autosomal dominant disorder typified by elevated low-density lipoprotein cholesterol (LDL-C) levels caused by mutations in the LDL receptor (LDLR), apolipoprotein B (ApoB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Previously, we reported a novel mutation in the exon-3 of LDLR gene, observed in a 9-year-old Omani Arab female. Here, we investigated the mode of inheritance of this mutation and confirmed that FH in this family is due to mutation only in the LDLR and not PCSK9 and ApoB genes. Further, the effect of the mutation has been appraised in silico on the tertiary structure of LDLR. A model of the mutant LDLR has been constructed using the coordinates of the wild-type LDLR extracellular domain. Based on the model, we present a mechanistic justification behind the observed detrimental effect of the mutation on LDL-C levels.

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Low-density lipoprotein receptor gene mutation analysis and structure-function correlation in an Omani Arab family with familial hypercholesterolemia

Abstract

Keywords

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