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PMID: 32655146 Published · ppublish English Journal Article

ALG3-CDG: lethal phenotype and novel variants in Chinese siblings.

Journal of human genetics ·Vol. 65 ·No. 12 ·2020-12-00 ·Pages 1129-1134

Bian Y, Qiao C, Zheng S, Qiu H, Li H, Zhang Z, Yin S, Jiang H, Li-Ling J, Liu C, Lyu Y

Abstract

Congenital disorders of glycosylation (CDG) are a group of genetic, mostly multisystem disorders, which often involve the central nervous system. ALG3-CDG is one the some 130 known CDG. Here we report two siblings with a severe phenotype and intrauterine death. Whole-exome sequencing revealed two novel variants in ALG3: NM_005787.6:c.512G>T (p.Arg171Leu) inherited from the mother and NM_005787.6:c.511C>T (p.Arg171Trp) inherited from the father.

MeSH Terms
Aborted Fetus/pathology Central Nervous System/metabolism,pathology Congenital Disorders of Glycosylation/genetics,metabolism,pathology Female Genes, Lethal/genetics Humans Male Mannosyltransferases/genetics Mothers Mutation/genetics Phenotype Siblings Whole Exome Sequencing
Chemicals
ALG3 protein, human Mannosyltransferases
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Bian Yue
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China. | Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Research Center of China Medical University Birth Cohort, Shenyang, China.
Qiao Chong
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China. | Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Research Center of China Medical University Birth Cohort, Shenyang, China.
Zheng ShuGuang
Department of Radiology, The People's Hospital of China Medical University, Shenyang, China.
Qiu Hao
Dian Diagnostics Group Co., LTD., Hangzhou, China.
Li Huan
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Zhang ZhiTao
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Yin ShaoWei
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Jiang HongKun
Department of Pediatrics, The First Affiliated Hospital of China Medical University, Shenyang, China.
Li-Ling Jesse
Jinxin Research Institute of Reproductive Medicine and Genetics, Jinjiang Maternal and Children's Health Care Hospital, Chengdu, China.
Liu CaiXia
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China. | Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Research Center of China Medical University Birth Cohort, Shenyang, China.
Lyu Yuan ORCID
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China. hawk.lv@163.com. | Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Research Center of China Medical University Birth Cohort, Shenyang, China. hawk.lv@163.com.
References (14)
14 references, click to expand
  1. Congenital disorders of glycosylation.
    Chang IJ, He M, Lam CT. Congenital disorders of glycosylation. Ann Transl Med. 2018;6:477. PMID: 30740408 DOI
  2. Congenital disorder of glycosylation type Id (CDG Id): phenotypic, biochemical and molecular characterization of a new patient.
    Rimella-Le-Huu A, Henry H, Kern I, Hanquinet S, Roulet-Perez E, Newman CJ. et al.Congenital disorder of glycosylation type Id (CDG Id): phenotypic, biochemical and molecular characterization of a new patient. J Inherit Metab Dis. 2008;31:S381–S6. PMID: 18679822 DOI
  3. Lepais L, Cheillan D, Frachon SC, Hays S, Matthijs G, Panagiotakaki E, et al. ALG3-CDG: report of two siblings with antenatal features carrying homozygous p.Gly96Arg mutation. Am J Med Genet A. 2015;167A:2748–54. DOI
  4. Kranz C, Sun L, Eklund EA, Krasnewich D, Casey JR, Freeze HH. CDG-Id in two siblings with partially different phenotypes. Am J Med Genet A. 2007;143A:1414–20. DOI
  5. Alsubhi S, Alhashem A, Faqeih E, Alfadhel M, Alfaifi A, Altuwaijri W, et al. Congenital disorders of glycosylation: the Saudi experience. Am J Med Genet A. 2017;173:2614–21. DOI
  6. Denecke J, Kranz C, von Kleist-Retzow JC, Bosse K, Herkenrath P, Debus O, et al. Congenital disorder of glycosylation type Id: clinical phenotype, molecular analysis, prenatal diagnosis, and glycosylation of fetal proteins. Pediatr Res. 2005;58:248–53. DOI
  7. Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase.
    Körner C, Knauer R, Stephani U, Marquardt T, Lehle L, von Figura K. Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase. EMBO J. 1999;18:6816–22. PMID: 10581255 DOI
  8. Riess S, Reddihough DS, Howell KB, Dagia C, Jaeken J, Matthijs G, et al. ALG3-CDG (CDG-Id): clinical, biochemical and molecular findings in two siblings. Mol Genet Metab. 2013;110:170–5. DOI
  9. Carbohydrate-deficient glycoprotein syndrome--a fourth subtype.
    Stibler H, Stephani U, Kutsch U. Carbohydrate-deficient glycoprotein syndrome–a fourth subtype. Neuropediatrics. 1995;26:235–7. PMID: 8552211 DOI
  10. Congenital disorder of glycosylation id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasia.
    Sun L, Eklund EA, Chung WK, Wang C, Cohen J, Freeze HH. Congenital disorder of glycosylation id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasia. J Clin Endocrinol Metab. 2005;90:4371–5. PMID: 15840742 DOI
  11. Electroclinical Features of Early-Onset Epileptic Encephalopathies in Congenital Disorders of Glycosylation (CDGs).
    Fiumara A, Barone R, Del Campo G, Striano P, Jaeken J. Electroclinical features of early-onset epileptic encephalopathies in congenital disorders of glycosylation (CDGs). JIMD Rep. 2016;27:93–9. PMID: 26453362 DOI
  12. Novel variants and clinical symptoms in four new ALG3-CDG patients, review of the literature, and identification of AAGRP-ALG3 as a novel ALG3 variant with alanine and glycine-rich N-terminus.
    Himmelreich N, Dimitrov B, Geiger V, Zielonka M, Hutter A-M, Beedgen L, et al. Novel variants and clinical symptoms in four new ALG3-CDG patients, review of the literature, and identification of AAGRP-ALG3 as a novel ALG3 variant with alanine and glycine-rich N-terminus. Hum Mutat. 2019;40:938–51. PMID: 31067009
  13. CDG-Id caused by homozygosity for an ALG3 mutation due to segmental maternal isodisomy UPD3(q21.3-qter).
    Schollen E, Grünewald S, Keldermans L, Albrecht B, Körner C, Matthijs G. CDG-Id caused by homozygosity for an ALG3 mutation due to segmental maternal isodisomy UPD3(q21.3-qter). Eur J Med Genet. 2005;48:153–8. PMID: 16053906 DOI
  14. An activated 5' cryptic splice site in the human ALG3 gene generates a premature termination codon insensitive to nonsense-mediated mRNA decay in a new case of congenital disorder of glycosylation type Id (CDG-Id).
    Denecke J, Kranz C, Kemming D, Koch H-G, Marquardt T. An activated 5’ cryptic splice site in the human ALG3 gene generates a premature termination codon insensitive to nonsense-mediated mRNA decay in a new case of congenital disorder of glycosylation type Id (CDG-Id). Hum Mutat. 2004;23:477–86. PMID: 15108280 DOI
Article Info
Journal
Journal of human genetics
Abbr.
J Hum Genet
ISSN
1435-232X
DOI
10.1038/s10038-020-0798-7
Email
hawk.lv@163.com
Published
2020-12-00
Epub
2020-00-12
Pages
1129-1134
Language
English
Region
England
NLM ID
9808008
PMCID
PMC7605439
Subset
IM
External Links
PubMed source DOI: 10.1038/s10038-020-0798-7 PMC Full Text View journal details
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