Genome sequencing reveals novel causative structural and single nucleotide variants in Pakistani families with congenital hypogonadotropic hypogonadism.
Details
Serval ID
serval:BIB_F2B039CA795D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome sequencing reveals novel causative structural and single nucleotide variants in Pakistani families with congenital hypogonadotropic hypogonadism.
Journal
BMC genomics
ISSN
1471-2164 (Electronic)
ISSN-L
1471-2164
Publication state
Published
Issued date
14/08/2024
Peer-reviewed
Oui
Volume
25
Number
1
Pages
787
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
This study aims to elucidate the genetic causes of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder resulting in GnRH deficiency, in six families from Pakistan.
Eighteen DNA samples from six families underwent genome sequencing followed by standard evaluation for pathogenic single nucleotide variants (SNVs) and small indels. All families were subsequently analyzed for pathogenic copy number variants (CNVs) using CoverageMaster.
Novel pathogenic homozygous SNVs in known CHH genes were identified in four families: two families with variants in GNRHR, and two others harboring KISS1R variants. Subsequent investigation of CNVs in the remaining two families identified novel unique large deletions in ANOS1.
A combined, systematic analysis of single nucleotide and CNVs helps to improve the diagnostic yield for variants in patients with CHH.
Eighteen DNA samples from six families underwent genome sequencing followed by standard evaluation for pathogenic single nucleotide variants (SNVs) and small indels. All families were subsequently analyzed for pathogenic copy number variants (CNVs) using CoverageMaster.
Novel pathogenic homozygous SNVs in known CHH genes were identified in four families: two families with variants in GNRHR, and two others harboring KISS1R variants. Subsequent investigation of CNVs in the remaining two families identified novel unique large deletions in ANOS1.
A combined, systematic analysis of single nucleotide and CNVs helps to improve the diagnostic yield for variants in patients with CHH.
Keywords
Humans, Hypogonadism/genetics, Pakistan, Male, Polymorphism, Single Nucleotide, Pedigree, Female, DNA Copy Number Variations, Receptors, Kisspeptin-1/genetics, Whole Genome Sequencing, Receptors, LHRH/genetics, Adult, Membrane Proteins/genetics, Nerve Tissue Proteins, Extracellular Matrix Proteins, Congenital hypogonadotropic hypogonadism, Copy number variants, Infertility, Rare endocrine disease, Whole genome sequencing
Pubmed
Web of science
Open Access
Yes
Create date
19/08/2024 9:20
Last modification date
20/08/2024 7:24