Title :

A PMM2-CDG caused by an A108V mutation associated with a heterozygous 70 kilobases deletion case report

Author(s) :

Lebredonchel, Elodie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Riquet, A. [Auteur]
Neut, D. [Auteur]
Broly, F. [Auteur]
Matthijs, G. [Auteur]
Klein, André [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Journal title :

Italian Journal of Pediatrics

Abbreviated title :

Ital J Pediatr

Volume number :

48

Publisher :

Springer Science and Business Media LLC

Publication date :

2022-10-11

ISSN :

1824-7288

English keyword(s) :

CDG
PMM2
Deletion mutation
PMM2-CDG
Whole genome sequencing

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

Background Congenital Disorders of Glycosylation (CDG) are a large group of inborn errors of metabolism with more than 140 different CDG types reported to date (1). The first characterized, PMM2-CDG, with an autosomal ...
Show more >Background Congenital Disorders of Glycosylation (CDG) are a large group of inborn errors of metabolism with more than 140 different CDG types reported to date (1). The first characterized, PMM2-CDG, with an autosomal recessive transmission, is also the most frequent. The PMM2 gene encodes a phosphomannomutase. Here, a novel genetic variation causing PMM2-CDG is reported.  Case presentation We report the case of a French child, from healthy and unrelated parents, presenting congenital ataxia with hypotonia, hyperlaxity, inverted nipples, as well as altered coagulation parameters and liver function. Transferrin isoelectrofocusing revealed a typical type I CDG profile. Direct Sanger sequencing and quantitative PCR of PMM2 revealed a unique and novel genotype. On one allele, the patient was heterozygote with a known missense variant NM_000303.3(PMM2):c.323C > T, p.Ala108Val in exon 4. On the second allele, whole genome sequencing (WGS) indicated the presence of a novel heterozygous 70 kb deletion. Conclusion We report in the present paper the largest known heterozygous deletion of a PMM2 gene. The observation reveals the impact of a precise diagnostic on genetic counselling: by using WGS, an erroneous conclusion of homozygosity in the case of a relatively rare variant could be avoided, and an index patient with healthy and unrelated parents correctly identified.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Mécanismes moléculaires de la N-glycosylation et pathologies associées

Submission date :

2022-11-16T14:27:47Z
2022-11-17T12:12:25Z