Recessive mutations in SLC35A3 cause early onset epileptic encephalopathy with skeletal defects

Marini C., Hardies K., Pisano T., May P., Weckhuysen S., Cellini E., ...Daha Fazla

American Journal of Medical Genetics, Part A, cilt.173, sa.4, ss.1119-1123, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 173 Sayı: 4
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1002/ajmg.a.38112
  • Dergi Adı: American Journal of Medical Genetics, Part A
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1119-1123
  • Anahtar Kelimeler: epileptic encephalopathy, genetics, infantile spasms, suppression burst, skeletal abnormalities, N-ACETYLGLUCOSAMINE TRANSPORTER, COMPLEX VERTEBRAL MALFORMATION, OF-FUNCTION MUTATIONS, GLYCOSYLATION, DISORDER, NOTCH, GENE
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

© 2017 Wiley Periodicals, Inc.We describe the clinical and whole genome sequencing (WGS) study of a non-consanguineous Italian family in which two siblings, a boy and a girl, manifesting a severe epileptic encephalopathy (EE) with skeletal abnormalities, carried novel SLC35A3 compound heterozygous mutations. Both siblings exhibited infantile spasms, associated with focal, and tonic vibratory seizures from early infancy. EEG recordings showed a suppression-burst (SB) pattern and multifocal paroxysmal activity in both. In addition both had quadriplegia, acquired microcephaly, and severe intellectual disability. General examination showed distal arthrogryposis predominant in the hands in both siblings and severe left dorso-lumbar convex scoliosis in one. WGS of the siblings-parents quartet identified novel compound heterozygous mutations in SLC35A3 in both children. SLC35A3 encodes the major Golgi uridine diphosphate N-acetylglucosamine transporter. With this study, we add SLC35A3 to the gene list of epilepsies. Neurological symptoms and skeletal abnormalities might result from impaired glycosylation of proteins involved in normal development and function of the central nervous system and skeletal apparatus.