NOTCH2 mutation in family 2. a, Proband, her mother, and her grandmother had clinical features associated with AGS. The family member marked with an asterisk (*) was tested for the presence of the mutation but had only wild-type sequence. Individuals marked with a section symbol (§) had mutant sequences. b, Sequence analysis shows a mutation in exon 8 in all three affected individuals. c, The mutation (asterisk) is predicted to cause substitution of a tyrosine for a cysteine residue in EGF-like repeat 11 of Notch2.

NOTCH2 mutation in family 1. a, Proband and his mother demonstrate features of AGS. Family members marked with an asterisk (*) were tested for the presence of the mutation but had only wild-type sequence. Individuals marked with a section symbol (§) had mutant sequences. b, Genomic DNA (gDNA) and cDNA sequencing demonstrates the presence and consequences of a mutation in the splice site of exon 33 in the proband and his mother. c, cDNA amplification and electrophoresis demonstrate the abnormally spliced product (arrow). d, Predicted protein product is represented below the diagram of the wild-type Notch2 protein (mutation marked by an asterisk). EGFR = EGF-like repeats.