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<p>N-glycanase1 (NGLY1) deficiency, an autosomal recessive disorder identified a decade ago, is categorized as a congenital disorder of deglycosylation (CDDG). This disorder arises from bi-allelic variants in the <i>NGLY1</i> gene, leading to impaired protein deglycosylation. Phenotypically, individuals with <i>NGLY1</i> deficiency present with intellectual disability, movement disorders, liver dysfunction, muscular hypotonia, etc., termed as NGLY1-CDDG, its diagnosis relies primarily on next generation sequencing (NGS) and till date, it has been diagnosed in over 100 patients. However, there are no previous reports on this from India. We report the first two <i>NGLY1</i> cases from India&#xa0;in this study. These patients presented with developmental delay, movement disorder, microcephaly, hypotonia and suspicion of congenital disorder of glycosylation (CDG) and were assessed for glycosylation defect using the high pressure liquid chromatography (HPLC) based transferrin isoform analysis and whole exome sequencing (WES). Both patients exhibited a normal transferrin isoform pattern and harboured variants in <i>NGLY1</i> gene. The variants, NM_018297.4:c.571C&gt;T; p.Gln191Ter and NM_018297.4:c.707G&gt;A; p.Trp236Ter on exons 4 and 5, respectively, identified in our patients are bi-allelic loss of function homozygous variants that have not been previously reported. These variants are inferred as pathogenic in view of genotype–phenotype correlation, parental segregation analysis, <i>in-silico</i> analyses, and absence of other genetic disorders. We have also summarized literature reports on NGLY1-CDDG and compared the phenotype and variants of our patients with the reported cases. These cases contribute to the clinical, biochemical, and molecular understanding of <i>NGLY1</i> deficiency among Indians, thereby elucidating the presence of NGLY1-CDDG in India.</p>

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NGLY1-CDDG: report of two cases from India and brief review of literature

  • 期刊论文

  • 发表日期：

    2025年7月28日

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  • Mihika B. Dave,
  • Vrajesh P. Udani,
  • Anaita U. Hegde,
  • Tester F. Ashavaid,
  • Alpa J. Dherai

摘要

N-glycanase1 (NGLY1) deficiency, an autosomal recessive disorder identified a decade ago, is categorized as a congenital disorder of deglycosylation (CDDG). This disorder arises from bi-allelic variants in the NGLY1 gene, leading to impaired protein deglycosylation. Phenotypically, individuals with NGLY1 deficiency present with intellectual disability, movement disorders, liver dysfunction, muscular hypotonia, etc., termed as NGLY1-CDDG, its diagnosis relies primarily on next generation sequencing (NGS) and till date, it has been diagnosed in over 100 patients. However, there are no previous reports on this from India. We report the first two NGLY1 cases from India in this study. These patients presented with developmental delay, movement disorder, microcephaly, hypotonia and suspicion of congenital disorder of glycosylation (CDG) and were assessed for glycosylation defect using the high pressure liquid chromatography (HPLC) based transferrin isoform analysis and whole exome sequencing (WES). Both patients exhibited a normal transferrin isoform pattern and harboured variants in NGLY1 gene. The variants, NM_018297.4:c.571C>T; p.Gln191Ter and NM_018297.4:c.707G>A; p.Trp236Ter on exons 4 and 5, respectively, identified in our patients are bi-allelic loss of function homozygous variants that have not been previously reported. These variants are inferred as pathogenic in view of genotype–phenotype correlation, parental segregation analysis, in-silico analyses, and absence of other genetic disorders. We have also summarized literature reports on NGLY1-CDDG and compared the phenotype and variants of our patients with the reported cases. These cases contribute to the clinical, biochemical, and molecular understanding of NGLY1 deficiency among Indians, thereby elucidating the presence of NGLY1-CDDG in India.