Figure 3

Figure 3

Identification of new VANGL2 germline variants and families. (A) Clinical pedigrees of putative recessive p.R135W VANGL2 family. Both deceased male probands (for which DNA was unavailable) possessed complete atrioventricular septal defect, respiratory distress syndrome, large occipital encephalocele and congenital hydrocephalus. Heterozygous family members were clinically normal. (B) Clinical pedigree of heterozygous p.R169H VANGL2 family. Antenatal diagnosis of male proband identified dextrocardia, persistent left superior vena cava, total anomalous pulmonary venous drainage, atrioventricular septal defect, transposition of great arteries, pulmonary atresia, right pulmonary isomerism and asplenia. The elder brother is also heterozygous with situs inversus. The heterozygous father was clinically normal. (C) Clinical pedigree of heterozygous p.E465A VANGL2 family in which proband has autosomal dominant non-syndromic hearing loss. The heterozygous p.E465A variant is also present in an unaffected relative. (D) Primary structure of Human VANGL2 showing known functional domains and location of previously reported and novel VUS reproduced from Fig. 2A. Squares, circles, diamonds, triangles represent male, females, unknown gender, and foetuses, respectively. Arrowheads denote proband. Diagonal line denotes deceased. Open symbols: healthy, black symbols: affected. Question mark denotes DNA unavailable. Het.: heterozygous, Hom: homozygous, TOP: termination of pregnancy.