Novel plasminogen gene mutations in Turkish patients with type I plasminogen deficiency.
The plasminogen (Plg) protein is the inactive proenzyme form of plasmin that dissolves fibrin thrombi by a process called fibrinolysis. It has been shown that homozygous or compound-heterozygous deficiency of this protein is a major cause of a rare inflammatory disease affecting mainly mucous membranes found in different body sites. In this study, five individual Turkish patients and nine Turkish families with type 1 Plg deficiency were investigated for PLG gene mutations. All of the coding regions of the PLG gene mutations were screened for mutations using denaturing high-pressure liquid chromatography (DHPLC). Samples showing a different DHPLC profile were subjected to DNA sequencing analysis. Here, we described five novel mutations namely, Cys49Ter, +1 IVS6 G>A, Gly218Val, Tyr283Cys, and Gly703Asp. Previously identified five nonsynonymous (Lys38Glu, Glu180Lys, Gly420Asp, Asp453Asn, Pro763Ser), five synonymous (330 C>T, 582 C>T, 771 T>C, 1083 A>G, 2286 T>G), and a 3' untranslated region (3' UTR) mutation (c.*45 A>G) were also reported in this present study. In this study, we have identified a total of eight mutations, five of which are novel. The mutations/polymorphisms identified in eight of the patients do not explain the disease phenotype. These cases probably carry other pathological mutations (homozygous or compound heterozygous) that cannot be detected by DHPLC.
aBiotechnology Institute, Ankara University, Ankara bDepartment of Pediatrics, İstanbul University, Cerrahpaşa Faculty of Medicine, İstanbul cDepartment of Pediatric Hematology, Kocaeli University Faculty of Medicine, Kocaeli dDepartment of Pediatric Neurology eDepartment of Pediatric Hematology, Ankara University Faculty of Medicine, Ankara fDepartment of Pediatrics, Necmettin Erbakan University Meram Faculty of Medicine, Konya gDepartment of Pediatrics, İstanbul Faculty of Medicine, İstanbul hDepartment of Pediatric Hematology, Çukurova University Faculty of Medicine, Adana iDepartment of Pediatrics, Akdeniz University Faculty of Medicine jDepartment of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey.
Buket
B
Dönmez-Demir
Tiraje
T
Celkan
Nazan
N
Sarper
Gülhis
G
Deda
Elif
E
İnce
Ümran
Ü
Çalişkan
Gülyüz
G
Öztürk
Barbaros
B
Karagün
Alphan
A
Küpesiz
Hüseyin
H
Tokgöz
Nejat
N
Akar
Hilal
H
Özdağ
D020413:3' Untranslated Regions; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003231:Conjunctivitis / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006849:Hydrocephalus / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D016366:Open Reading Frames; D010641:Phenotype; D010958:Plasminogen / Q000172:deficiency* / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012873:Skin Diseases, Genetic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D014421:Turkey
D020413:3' Untranslated Regions; D010958:Plasminogen