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

• Auteurs principaux: E. Lebredonchel (Auteur), A. Riquet (Auteur), D. Neut (Auteur), F. Broly (Auteur), G. Matthijs (Auteur), A. Klein (Auteur), F. Foulquier (Auteur)
• Format: Livre
• Publié: BMC, 2022-10-01T00:00:00Z.
• Sujets: article
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Résumé

Abstract 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.

Description

10.1186/s13052-022-01355-x
1824-7288