A Novel Deletion in FERMT3 Causes LAD-III in a Turkish Family

Köker N., Deveci İ., Van Leeuwen K., Akbayram S., Roos D., Kuijpers T. W., ...Daha Fazla

Journal of Clinical Immunology, cilt.43, sa.4, ss.741-746, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 43 Sayı: 4
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1007/s10875-022-01420-4
  • Dergi Adı: Journal of Clinical Immunology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.741-746
  • Anahtar Kelimeler: Primary immunodeficiency, leukocyte adhesion deficiency, kindlin-3, integrin, FERMT3
  • Erciyes Üniversitesi Adresli: Evet

Özet

Leukocyte adhesion deficiency-III (LAD-III) is an extremely rare autosomal recessive syndrome caused by mutations in FERMT3, the gene encoding kindlin-3. The genetic alterations in this gene lead to abnormal expression or activity of kindlin-3 in leukocytes and platelets. Kindlin-3 acts as an important regulator of integrin activation. LAD-III has features of the bleeding syndrome of Glanzmann and also of leukocyte adhesion deficiency. In this study, we report on two families, one of Turkish and one of Syrian origin, with clinical features of LAD-III, loss of kindlin-3 protein expression, and a functional leukocyte defect. A novel, homozygous deletion in FERMT3 (c.921delC, p.Ser307Argfs*21) was found in the Turkish patient. The parents were carriers of the mutation, consistent with an autosomal recessive inheritance. A common c.1525C > T (p.Arg509*) mutation was found in the Syrian patient. In conclusion, beside the variant c.1525C > T in the FERMT3 gene, which was previously found in more than 15 patients in Anatolia, our study is the first to identify the novel homozygous variant c.921delC in the FERMT3 gene.