Figure 6. Identification of novel ACE mutation- Ser333Trp.

A. Sequencing of ACE gene in patient # 27. Heterozygous mutation Ser333Trp (S333W) in 7^th exon was revealed by the sequencing 6–12^th, 19^th–24th exons of ACE gene of this patient. B. Alignment of amino acid sequences from ACE of several vertebrate species indicates that S333 and the flanking residues are highly conserved. The numbering relates to the mature ACE. C. Family tree of patient # 27 with new (S333W) mutation in ACE gene. Genotyped individual with S333W mutation are indicated by yellow color. Individuals found to have low value of ZPHL/HHL ratio for serum ACE are marked by upward pointing arrows. Following abbreviations are used for known clinical diagnoses: SCD-Sickle Cell Disease, DM–diabetes mellitus, HTN–hypertension. Among individuals in whom both genotyping and serum ACE determination was performed, there was 100% concordance between presence or absence of the S333W mutation and low or non-elevated ZPHL/HHL ratio for serum ACE, respectively.