Characterization of 11 new cases of leukocyte adhesion deficiency type 1 with seven novel mutations in the ITGB2 gene.
BACKGROUND
Leukocyte adhesion deficiency type 1 (LAD I) is an autosomal recessive disorder caused by mutations in the ITGB2 gene, encoding the beta2 integrin family. Severe recurrent infections, impaired wound healing, and periodontal diseases are the main features of disease.


METHODS
In order to investigate clinical and molecular manifestations of new LAD I cases, 11 patients diagnosed in one center during 7 years were studied. Patients were screened for the ITGB2 gene mutations, using polymerase chain reaction, followed by single-strand conformation polymorphism and sequencing.


RESULTS
The most common first presenting feature of the patients was omphalitis. The mean age of cord separation was 19.9 +/- 1 days. The most common clinical manifestations of the patients during the follow-up period included omphalitis, skin ulcers with poor healing, sepsis, and otitis media. During the follow-up, eight patients died. Eight homozygous changes, including seven novel mutations, were detected: two splicing (IVS4-6C>A, IVS7+1G>A), three missense (Asp128Tyr, Ala239Thr, and Gly716Ala), and three frameshift deletions (Asn282fsX41, Tyr382fsX9, and Lys636fsX22).


CONCLUSIONS
Our results indicate that different mutations underlie the development of LAD I. Definitive molecular diagnosis is valuable for genetic counseling and prenatal diagnosis. Regarding clinical presentations, it seems that omphalitis is the most consistent finding seen in LAD I infants.
Parvaneh
Nima
N
Infectious Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran. nparvaneh@tums.ac.ir
Mamishi
Setareh
S
Rezaei
Amir
A
Rezaei
Nima
N
Tamizifar
Banafshe
B
Parvaneh
Leila
L
Sherkat
Roya
R
Ghalehbaghi
Babak
B
Kashef
Sara
S
Chavoshzadeh
Zahra
Z
Isaeian
Anna
A
Ashrafi
Farzaneh
F
Aghamohammadi
Asghar
A
D000595:Amino Acid Sequence; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D016905:Gram-Negative Bacterial Infections / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007492:Iran; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D012008:Recurrence; D012883:Skin Ulcer / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D014470:Umbilical Cord / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
D003598:Cytoskeletal Proteins; C492400:ITGB1BP2 protein, human; D009124:Muscle Proteins