Novel form of rhizomelic skeletal dysplasia associated with a homozygous variant in
Adult
Aged
Aged, 80 and over
Animals
Bone Diseases, Developmental
/ diagnostic imaging
Cells, Cultured
Consanguinity
Female
Femur
/ abnormalities
Glucosamine 6-Phosphate N-Acetyltransferase
/ genetics
Homozygote
Humans
Humerus
/ abnormalities
Male
Middle Aged
Pedigree
Radiography
Rats, Sprague-Dawley
cell biology
genetics
molecular genetics
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
20
02
2020
revised:
18
05
2020
accepted:
21
05
2020
pubmed:
28
6
2020
medline:
19
1
2022
entrez:
28
6
2020
Statut:
ppublish
Résumé
Studies exploring molecular mechanisms underlying congenital skeletal disorders have revealed novel regulators of skeletal homeostasis and shown protein glycosylation to play an important role. To identify the genetic cause of rhizomelic skeletal dysplasia in a consanguineous Pakistani family. Clinical investigations were carried out for four affected individuals in the recruited family. Whole genome sequencing (WGS) was completed using DNA from two affected and two unaffected individuals from the family. Sequencing data were processed, filtered and analysed. In silico analyses were performed to predict the effects of the candidate variant on the protein structure and function. Small interfering RNAs (siRNAs) were used to study the effect of The patients presented with short stature due to extreme shortening of the proximal segments of the limbs. Radiographs of one individual showed hip dysplasia and severe platyspondyly. WGS data analyses identified a homozygous missense variant c.226G>A; p.(Glu76Lys) in This study describes a novel severe skeletal dysplasia associated with a biallelic, variant in
Sections du résumé
BACKGROUND
Studies exploring molecular mechanisms underlying congenital skeletal disorders have revealed novel regulators of skeletal homeostasis and shown protein glycosylation to play an important role.
OBJECTIVE
To identify the genetic cause of rhizomelic skeletal dysplasia in a consanguineous Pakistani family.
METHODS
Clinical investigations were carried out for four affected individuals in the recruited family. Whole genome sequencing (WGS) was completed using DNA from two affected and two unaffected individuals from the family. Sequencing data were processed, filtered and analysed. In silico analyses were performed to predict the effects of the candidate variant on the protein structure and function. Small interfering RNAs (siRNAs) were used to study the effect of
RESULTS
The patients presented with short stature due to extreme shortening of the proximal segments of the limbs. Radiographs of one individual showed hip dysplasia and severe platyspondyly. WGS data analyses identified a homozygous missense variant c.226G>A; p.(Glu76Lys) in
CONCLUSIONS
This study describes a novel severe skeletal dysplasia associated with a biallelic, variant in
Identifiants
pubmed: 32591345
pii: jmedgenet-2020-106929
doi: 10.1136/jmedgenet-2020-106929
doi:
Substances chimiques
GNPNAT1 protein, human
EC 2.3.1.4
Glucosamine 6-Phosphate N-Acetyltransferase
EC 2.3.1.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
351-356Informations de copyright
© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.