2. Academic Validation
  3. Recessive mutations in SCYL2 cause a novel syndromic form of arthrogryposis in humans

Recessive mutations in SCYL2 cause a novel syndromic form of arthrogryposis in humans

  • Hum Genet. 2020 Apr;139(4):513-519. doi: 10.1007/s00439-020-02117-7.
Mohammed Zain Seidahmed 1,  Adila Al-Kindi 2 3,  Hessa S Alsaif 4,  Abeer Miqdad 1,  Nasser Alabbad 5,  Abdallah Alfifi 1,  Omer Bashir Abdelbasit 1,  Khalid Alhussein 1,  Abdulmohsen Alsamadi 1,  Niema Ibrahim 4,  Amna Al-Futaisi 6,  Almundher Al-Maawali 7 8,  Fowzan S Alkuraya 9 10
Affiliations

Affiliations

  • 1 Deparment of Pediatrics, Security Forces Hospital, Riyadh, Saudi Arabia.
  • 2 Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
  • 3 Genetic and Developmental Medicine Clinic, Sultan Qaboos University Hospital, Muscat, Oman.
  • 4 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • 5 Department of Obstetrics and Gynaecology, Security Forces Hospital, Riyadh, Saudi Arabia.
  • 6 Department of Child Health, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
  • 7 Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman. almaawali@squ.edu.om.
  • 8 Genetic and Developmental Medicine Clinic, Sultan Qaboos University Hospital, Muscat, Oman. almaawali@squ.edu.om.
  • 9 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.
  • 10 Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.
PMID: 31960134 DOI: 10.1007/s00439-020-02117-7
Abstract

Arthrogryposis multiplex congenita (AMC) is an important birth defect with a significant genetic contribution. Many syndromic forms of AMC have been described, but remain unsolved at the molecular level. In this report, we describe a novel syndromic form of AMC in two multiplex consanguineous families from Saudi Arabia and Oman. The phenotype is highly consistent, and comprises neurogenic arthrogryposis, microcephaly, brain malformation (absent corpus callosum), optic atrophy, limb fractures, profound global developmental delay, and early lethality. Whole-exome Sequencing revealed a different homozygous truncating variant in SCYL2 in each of the two families. SCYL2 is a component of clathrin-coated vesicles, and deficiency of its mouse ortholog results in a severe neurological phenotype that largely recapitulates the phenotype observed in our patients. Our results suggest that severe neurogenic arthrogryposis with brain malformation is the human phenotypic consequence of SCYL2 loss of function mutations.

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