Case# III-1, Female, Caucasian

CasePresentingHPOs HP:0001643

CaseMethod1 WES

CaseMethod2 PCR

Variant NM_001136239.3(PRDM6):c.788G>C (p.Cys263Ser)

ClinVar 243050

VariantEvidence Functional in vitro characterization of PRDM6 p.Cys263Ser in HEK293 cells and human aortic VSMCs showed that the variant protein significantly loses its capability for nuclear localization (Fig 3). DNA overexpression in adenovirus virus infected WT and mutant variants showed MYH11 is also not suppressed by mutant where it is suppressed in WT (Figure 4). Immunoblots of histones in WT human aortic smooth muscle transfected with the variant showed reduced histone modification and and suppression of contractile proteins. (Fig. 5)

Family#PresentingHPOs HP:0001643

CountryOrigin Africa

Ethnicity Nonhispanic

Race Black

Family#Method1 WES

Family#Method2 Sanger

Family#GenotypingMethod PCR of 180k exons of 18,673 protein-coding genes, genome-wide linkage analysis was performed on the family along with WES on subjects III-2, IV-9, III-11 and IV-6

Affected 10

Unaffected 5

Segregations 8

PublishedLOD 2.57

AddSegregationInfo incomplete pentrance

ProbandLabel PDA-101:III-2, Female

Variant NM_001136239.3(PRDM6):c.1646G>A (p.Arg549Gln)

ClinVar 243049

VariantEvidence Functional in vitro characterization of PRDM6 p.Arg549Gln in HEK293 cells and human aortic VSMCs showed that the variant protein significantly loses its capability for nuclear localization (Fig 3). DNA overexpression in adenovirus virus infected WT and mutant variants showed MYH11 is also not suppressed by mutant where it is suppressed in WT (Figure 4).

Case# II-1, Female, Caucasian

CasePresentingHPOs HP:0001643

CaseMethod1 WES

CaseMethod2 PCR

Variant NM_001136239.3(PRDM6):c.1385A>G (p.Gln462Arg)

ClinVar 243051

gnomAD 0.00001728 (European (Non-Finnish))

VariantEvidence no variant evidence, computational