A founder effect of c.1938delC in ITGB4 underlies junctional epidermolysis bullosa and its application for prenatal testing.
Junctional epidermolysis bullosa associated with pyloric atresia (JEB-PA) is one of the most severe inherited skin diseases, characterized by generalized blister formation and occlusion of the pylorus at birth. Most JEB-PA patients have mutations in the gene encoding β4 integrin (ITGB4). No recurrent mutations in ITGB4 have been described as having founder effects. We collected three JEB-PA families with c.1938delC in ITGB4. Haplotype analysis using single nucleotide polymorphism markers throughout ITGB4 suggested one rare haplotype (2.8% of the Han Chinese and ethnic Japanese populations) in all alleles with c.1938delC. The parents of one of the three families sought prenatal diagnosis for a subsequent pregnancy. We succeeded in performing prenatal exclusion of JEB-PA using the foetal genomic DNA. Our study clearly demonstrated that recurrent c.1938delC in ITGB4 is a founder mutation in JEB-PA patients, and that genotyping of the mutation can be utilized for prenatal diagnosis of JEB-PA.
Ken
K
Natsuga
Wataru
W
Nishie
Satoru
S
Shinkuma
Hideki
H
Nakamura
Ken
K
Arita
Kozo
K
Yoneda
Takashi
T
Kusaka
Toshihiro
T
Yanagihara
Rika
R
Kosaki
Haruhiko
H
Sago
Masashi
M
Akiyama
Hiroshi
H
Shimizu
D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D004252:DNA Mutational Analysis; D016109:Epidermolysis Bullosa, Junctional / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D039663:Integrin beta4 / Q000235:genetics*; D007564:Japan; D008297:Male; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017384:Sequence Deletion
C059834:ITGB4 protein, human; D039663:Integrin beta4