A novel variant in GNPNAT1 gene causing a spondylo-epi-metaphyseal dysplasia resembling PGM3-Desbuquois like dysplasia.
GNPNAT1
PGM3
SEMD
whole exome sequencing
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
17
05
2022
received:
30
03
2022
accepted:
11
06
2022
entrez:
13
9
2022
pubmed:
14
9
2022
medline:
15
9
2022
Statut:
ppublish
Résumé
Spondylo-epi-metaphyseal dysplasias (SEMDs) are a clinically and genetically heterogeneous group of skeletal dysplasias characterized by short stature and abnormal modeling of the spine and long bones. A novel form of rhizomelic skeletal dysplasia, Ain-Naz type, associated with a homozygous variant in GNPNAT1 was recently identified. Herein, we report an Egyptian patient, offspring of consanguineous parents, who presented with a severe form of unclassified SEMD. Whole exome sequencing identified a novel homozygous variant in exon 3, c.77T>G, (p.Phe26Cys) in GNPNAT1, that was confirmed by Sanger sequencing and both parents were found to be heterozygous for the identified variant. Main features included severe short stature, rhizomelic limb shortening, and wide flared metaphysis. Short broad long bones, brachydactyly, delayed epiphyseal ossification of long bones, advanced bone age, and immunodeficiency were additional findings expanding the clinical phenotype described in the previously reported family. We conclude that variants in the GNPNAT1 gene cause an autosomal recessive form of SEMD resembling Desbuquois like dysplasia caused by PGM3, which is involved in the same pathway as GNPNAT1.
Identifiants
pubmed: 36097642
doi: 10.1002/ajmg.a.62933
doi:
Substances chimiques
GNPNAT1 protein, human
EC 2.3.1.4
Glucosamine 6-Phosphate N-Acetyltransferase
EC 2.3.1.4
PGM3 protein, human
EC 5.4.2.2
Phosphoglucomutase
EC 5.4.2.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2861-2868Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
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