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Publications

Journal Article Epublish

PubMed: 42853272 DOI: 10.1007/s00439-026-02881-y

Clinical and molecular spectrum of congenital disorders of glycosylation in 80 Egyptian patients.

Hum Genet 145(1)

Authors: Mohamed S Abdel-Hamid, Sherif F Abdel-Ghafar, Mahmoud Y Issa, Walaa ElNaggar, Hasnaa M Elbendary, Karima Rafat, Nagwa Gaboon, Mahmoud M Noureldeen, Ziad N Rezk, Nour Elkhateeb, Laila Selim, Joseph G Gleeson, Maha S Zaki

Affiliations

  • Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre , Cairo, 12622, Egypt.
  • Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre , Cairo, 12622, Egypt.
  • Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, 12622, Egypt.
  • Leeds Clinical Genomic Service, Leeds Teaching Hospital Trust, Leeds, UK.
  • Department of Pediatrics, Pediatric Neurology and Metabolic Division, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt.
  • Medical Genetics Centre, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Medical Genetics Department, Armed Forces College of Medicine, Cairo, Egypt.
  • Department of Pediatrics, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.
  • Medical Genetics Department, Armed Forces College of Medicine, Cairo, Egypt.
  • Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • Department of Neurosciences, University of California, San Diego, La Jolla, USA.
  • Rady Children's Hospital, Rady Children's Institute for Genomic Medicine, San Diego, La Jolla, USA.
  • Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, 12622, Egypt.
  • Medical Genetics Department, Armed Forces College of Medicine, Cairo, Egypt.

Abstract

Congenital disorders of glycosylation (CDG) represent a diverse group of inborn errors of metabolism caused by defective glycosylation processes, usually characterized by multiorgan involvement and overlapping clinical symptoms. This study aimed to decipher the clinical and genetic landscape of CDG in Egypt to enumerate the most common CDG types and unveil potentially new candidate genes. The study included 80 patients from 57 families with molecular findings consistent with CDG. Consanguinity was noted in 90% of the families. The most common clinical features were global developmental delay (98%), dysmorphic facies (86%), hypotonia (85%), movement disorders (48%), and seizures (42%). Vision impairment, hepatic, skeletal, and hematological abnormalities were the most frequently encountered systemic manifestations. Structural brain anomalies were commonly observed in our cohort and included thin corpus callosum, cortical atrophy, white matter abnormalities, cerebellar atrophy, and cerebellar vermis hypoplasia. Biallelic variants were identified in 94% of patients, while 6% had variants in X-linked genes. A total of 53 variants were identified in 29 genes, of which 38 (72%) were novel. The most frequent variants were in SRD5A3 (16%), PMM2 (11%), ALG1 (10%), NGLY1 (7.5%), MGAT2 (6%), and ALG11 (5%). We identified two sibs with a homozygous missense variant in CAMLG, which has been recently described in only one case, supporting its role as a new CDG type. Additionally, we described a case with the recently reported UGGT1-CDG and proposed ALG10 as a potentially new CDG gene. Our study highlights the striking phenotypic and genotypic variability associated with CDG and broadens the spectrum of variants and causative genes.

MeSH

Genes, Atrophy, Congenital Disorders Of Glycosylation, Signs And Symptoms, Genetics, Medical, Genes, X-Linked