A PMM2-CDG caused by an A108V mutation associated with a heterozygous 70 kilobases deletion case report
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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-10-01
|
| Series: | Italian Journal of Pediatrics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13052-022-01355-x |
| _version_ | 1828103570731302912 |
|---|---|
| author | E. Lebredonchel A. Riquet D. Neut F. Broly G. Matthijs A. Klein F. Foulquier |
| author_facet | E. Lebredonchel A. Riquet D. Neut F. Broly G. Matthijs A. Klein F. Foulquier |
| author_sort | E. Lebredonchel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:28:13Z |
| format | Article |
| id | doaj.art-a9ad10d6713d40e2927940e39a912ee8 |
| institution | Directory Open Access Journal |
| issn | 1824-7288 |
| language | English |
| last_indexed | 2024-04-11T09:28:13Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Italian Journal of Pediatrics |
| spelling | doaj.art-a9ad10d6713d40e2927940e39a912ee82022-12-22T04:31:58ZengBMCItalian Journal of Pediatrics1824-72882022-10-014811510.1186/s13052-022-01355-xA PMM2-CDG caused by an A108V mutation associated with a heterozygous 70 kilobases deletion case reportE. Lebredonchel0A. Riquet1D. Neut2F. Broly3G. Matthijs4A. Klein5F. Foulquier6UMR 8576, Univ. Lille, CNRS, UGSF - Unité de Glycobiologie Structurale Et FonctionnelleLille University Hospital Center PaediatricsCabinet de PédiatrieCentre Hospitalier Régional Universitaire de Lille Centre de Biologie PathologieLaboratory for Molecular Diagnosis, Center for Human GeneticsUMR 8576, Univ. Lille, CNRS, UGSF - Unité de Glycobiologie Structurale Et FonctionnelleUMR 8576, Univ. Lille, CNRS, UGSF - Unité de Glycobiologie Structurale Et FonctionnelleAbstract 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.https://doi.org/10.1186/s13052-022-01355-xCDGPMM2Deletion mutationPMM2-CDGWhole genome sequencing |
| spellingShingle | E. Lebredonchel A. Riquet D. Neut F. Broly G. Matthijs A. Klein F. Foulquier A PMM2-CDG caused by an A108V mutation associated with a heterozygous 70 kilobases deletion case report Italian Journal of Pediatrics CDG PMM2 Deletion mutation PMM2-CDG Whole genome sequencing |
| title | A PMM2-CDG caused by an A108V mutation associated with a heterozygous 70 kilobases deletion case report |
| title_full | A PMM2-CDG caused by an A108V mutation associated with a heterozygous 70 kilobases deletion case report |
| title_fullStr | A PMM2-CDG caused by an A108V mutation associated with a heterozygous 70 kilobases deletion case report |
| title_full_unstemmed | A PMM2-CDG caused by an A108V mutation associated with a heterozygous 70 kilobases deletion case report |
| title_short | A PMM2-CDG caused by an A108V mutation associated with a heterozygous 70 kilobases deletion case report |
| title_sort | pmm2 cdg caused by an a108v mutation associated with a heterozygous 70 kilobases deletion case report |
| topic | CDG PMM2 Deletion mutation PMM2-CDG Whole genome sequencing |
| url | https://doi.org/10.1186/s13052-022-01355-x |
| work_keys_str_mv | AT elebredonchel apmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT ariquet apmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT dneut apmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT fbroly apmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT gmatthijs apmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT aklein apmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT ffoulquier apmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT elebredonchel pmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT ariquet pmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT dneut pmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT fbroly pmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT gmatthijs pmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT aklein pmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport AT ffoulquier pmm2cdgcausedbyana108vmutationassociatedwithaheterozygous70kilobasesdeletioncasereport |