TY - JOUR
T1 - A Novel Deletion in FERMT3 Causes LAD-III in a Turkish Family
AU - K?ker, Nezihe
AU - Deveci, ?hsan
AU - van Leeuwen, Karin
AU - Akbayram, Sinan
AU - Roos, Dirk
AU - Kuijpers, Taco W.
AU - K?ker, Mustafa Yavuz
N1 - Funding Information: This work was supported by the Erciyes University [BAP-TYL-2020–10064]. Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - FERMT3
KW - Primary immunodeficiency
KW - integrin
KW - kindlin-3
KW - leukocyte adhesion deficiency
UR - http://www.scopus.com/inward/record.url?scp=85146544414&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s10875-022-01420-4
DO - https://doi.org/10.1007/s10875-022-01420-4
M3 - Article
C2 - 36648575
SN - 0271-9142
VL - 43
SP - 741
EP - 746
JO - Journal of clinical immunology
JF - Journal of clinical immunology
IS - 4
ER -