Three novel mutations of the IRF6 gene with one associated with an unusual feature in Van der Woude syndrome.
Van der Woude syndrome (VWS) is a dominantly inherited disorder characterized by cleft lip with or without cleft palate and lip pits. It remains the most common syndromic form of oral clefts. Mutations in the interferon regulatory factor 6 (IRF6) gene have been identified in patients with VWS. We reported three unrelated families with lower lip anomalies. Two had lower lip pits, a cardinal sign of VWS, but the other had a heart-shaped mass on lower lip without pits, oral clefts, or hypodontia. This isolated anomaly has not been previously observed in VWS. We performed mutation analysis by PCR-sequencing the entire coding region of the IRF6 gene. Three potentially pathogenic mutations, c.145C>T (p.Q49X), c.171T>G (p.F57L), and 1306C>G (p.L436V) were successfully identified. All the missense mutations were not detected in 100 unaffected ethnic-matched control chromosomes and have never been previously reported. The p.Q49X and p.F57L mutations were located in the highly conserved DNA binding domain while the p.L436V was located at the carboxy-terminal region. This study reported an undescribed clinical feature of VWS and three novel mutations, expanding the phenotypic spectrum of VWS and mutational spectrum of IRF6.
Yeetong
Patra
P
Graduate School, Inter-Department Program of Biomedical Science, Chulalongkorn University, Bangkok, Thailand.
Mahatumarat
Charan
C
Siriwan
Pichit
P
Rojvachiranonda
Nond
N
Suphapeetiporn
Kanya
K
Shotelersuk
Vorasuk
V
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D050835:Interferon Regulatory Factors / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013577:Syndrome; D013785:Thailand
C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors