A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family.
Adult
Amelogenesis Imperfecta
/ epidemiology
Antiporters
/ genetics
Codon, Nonsense
/ genetics
Dental Caries
/ epidemiology
Dental Enamel
/ metabolism
Exons
/ genetics
Female
Genetic Predisposition to Disease
Humans
Male
Morphogenesis
/ genetics
Pakistan
/ epidemiology
Pedigree
Tooth Loss
/ genetics
Exome Sequencing
Young Adult
Amelogenesis imperfecta
Exome sequencing
Non-syndromic
Nonsense variant
SLC24A4
Journal
BMC medical genetics
ISSN: 1471-2350
Titre abrégé: BMC Med Genet
Pays: England
ID NLM: 100968552
Informations de publication
Date de publication:
07 05 2020
07 05 2020
Historique:
received:
14
10
2019
accepted:
28
04
2020
entrez:
9
5
2020
pubmed:
10
5
2020
medline:
17
7
2020
Statut:
epublish
Résumé
Amelogenesis imperfecta (AI) is a highly heterogeneous group of hereditary developmental abnormalities which mainly affects the dental enamel during tooth development in terms of its thickness, structure, and composition. It appears both in syndromic as well as non-syndromic forms. In the affected individuals, the enamel is usually thin, soft, rough, brittle, pitted, chipped, and abraded, having reduced functional ability and aesthetics. It leads to severe complications in the patient, like early tooth loss, severe discomfort, pain, dental caries, chewing difficulties, and discoloration of teeth from yellow to yellowish-brown or creamy type. The study aimed to identify the disease-causing variant in a consanguineous family. We recruited a consanguineous Pashtun family of Pakistani origin. Exome sequencing analysis was followed by Sanger sequencing to identify the pathogenic variant in this family. Clinical analysis revealed hypomaturation AI having generalized yellow-brown or creamy type of discoloration in affected members. We identified a novel nonsense sequence variant c.1192C > T (p.Gln398*) in exon-12 of SLC24A4 by using exome sequencing. Later, its co-segregation within the family was confirmed by Sanger sequencing. The human gene mutation database (HGMD, 2019) has a record of five pathogenic variants in SLC24A4, causing AI phenotype. This nonsense sequence variant c.1192C > T (p.Gln398*) is the sixth disease-causing variant in SLC24A4, which extends its mutation spectrum and confirms the role of this gene in the morphogenesis of human tooth enamel. The identified variant highlights the critical role of SLC24A4 in causing a rare AI type in humans.
Sections du résumé
BACKGROUND
Amelogenesis imperfecta (AI) is a highly heterogeneous group of hereditary developmental abnormalities which mainly affects the dental enamel during tooth development in terms of its thickness, structure, and composition. It appears both in syndromic as well as non-syndromic forms. In the affected individuals, the enamel is usually thin, soft, rough, brittle, pitted, chipped, and abraded, having reduced functional ability and aesthetics. It leads to severe complications in the patient, like early tooth loss, severe discomfort, pain, dental caries, chewing difficulties, and discoloration of teeth from yellow to yellowish-brown or creamy type. The study aimed to identify the disease-causing variant in a consanguineous family.
METHODS
We recruited a consanguineous Pashtun family of Pakistani origin. Exome sequencing analysis was followed by Sanger sequencing to identify the pathogenic variant in this family.
RESULTS
Clinical analysis revealed hypomaturation AI having generalized yellow-brown or creamy type of discoloration in affected members. We identified a novel nonsense sequence variant c.1192C > T (p.Gln398*) in exon-12 of SLC24A4 by using exome sequencing. Later, its co-segregation within the family was confirmed by Sanger sequencing. The human gene mutation database (HGMD, 2019) has a record of five pathogenic variants in SLC24A4, causing AI phenotype.
CONCLUSION
This nonsense sequence variant c.1192C > T (p.Gln398*) is the sixth disease-causing variant in SLC24A4, which extends its mutation spectrum and confirms the role of this gene in the morphogenesis of human tooth enamel. The identified variant highlights the critical role of SLC24A4 in causing a rare AI type in humans.
Identifiants
pubmed: 32380970
doi: 10.1186/s12881-020-01038-6
pii: 10.1186/s12881-020-01038-6
pmc: PMC7206816
doi:
Substances chimiques
Antiporters
0
Codon, Nonsense
0
SLC24A4 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
97Subventions
Organisme : Higher Education Commision, Pakistan
ID : 4857/NRPU/R&D/HEC2014
Pays : International
Organisme : Alexander von Humboldt-Stiftung
ID : 2015-2018
Pays : International
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