eISSN: 2083-8441
ISSN: 2081-237X
Pediatric Endocrinology Diabetes and Metabolism
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1/2021
vol. 27
 
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abstract:
Original paper

Characterisation of LDL receptor gene mutations in a North Indian cohort of children with homozygous familial hypercholesterolaemia

Shagun Singh
1
,
Minu Singh
1
,
Devi Dayal
1
,
Prateek Bhatia
1
,
Sandeep Negi
1
,
Savita V. Attri
1

1.
Department of Pediatrics, Postgraduate Institute of Medical Education and Research, India
Pediatr Endocrinol Diabetes Metab 2021; 27 (1): 32–36
Online publish date: 2021/02/11
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Introduction
Homozygous familial hypercholesterolaemia (HoFH) carries a grave prognosis but is often underdiagnosed and undertreated. Confirmation of molecular diagnosis helps in planning effective management and determining prognosis accurately. Aim of the study: To determine the spectrum of mutations in the LDLR gene in a cohort of children with a clinical diagnosis of HoFH.

Material and methods
Genomic DNA was extracted from peripheral blood samples of 8 patients, who were children of either sex, aged under 16 years, and diagnosed clinically with HoFH using the Simon Broome criteria. The potential variants in the LDLR gene were analysed by Sanger sequencing.

Results
Fifty variations were found in the 8 patients; 39 (78%) were single nucleotide variations while 8 (16%) and 3 (6%) were deletions and insertions, respectively. The pathogenic variants in the LDLR gene were detected in four patients; three showed duplication in exon 17 (c.2416dupG) creating an amino acid change at position 806 (p.Val806GlyfsTer11) while one had a missense variant in the exon 9 at position c.1285G>A resulting in a change in amino acid at position 429 (p.Val429Met). The variants were found in heterozygous state in the parents or siblings of probands who showed pathogenic variants.

Conclusions
The frequency of disease-causing variants in the LDLR gene in our patients with HoFH was 50%. Further studies to characterise mutations in genes for apolipoprotein B, proprotein convertase subtilisin/kexin type 9, or LDL adaptor protein are suggested in all children with a clinical diagnosis of HoFH.

keywords:

homozygous familial hypercholesterolaemia, LDLR gene, pathogenic variants, Indian families

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