1 reinhoff berkeley july 2010

LDS

BEALS blue sclerae

large joint PDA, VSD, ASD vascular tortuosity

contractures hypertelorism

ear deformity camptodactyly bifid uvula

arachnodactly

MVP joint laxity aortic dilitation hypomyoplasia scoliosis

dolichostenomelia pectus deformity

pes planus

lens dislocation

MFS

Parents: the Filter for New Variants in the Child

3MVariants/g

91-238New Variations/g/gen

Genetics 2000:156, 297-304 Curr. Biol. 2009:19, 1-5

Allele Specific Expression, CPNE1

15 C

0 G

6 C

58 G

5 C

50 G

Mother FatherChild

Inserted T in CPNE1results in truncated protein and loss of VWA protein domain

WT CPNE1

Daughter

Mother

Father

reference

reference

reference

WT CPNE1

Inserted T in CPNE1

• Jay Flatley

• Gary Schroth

• Irina Khrebtukova

• Steffen Durinck

• Shujun Luo

• Kevin Gunderson

• Ray McCauley

• Chris Burge

• Vincent Butty

• John Cleary

• Roni Cohen

• Marc Vidal

• Tong Hao

• Andy Fire

• Amy Chen

• Nick Okasinski

• Julie Yu

• Alan Littleford

• Se-Jin Lee

• Nazli MacDonald

• John Sotos

• Alan Beggs

• David Clapham

• Hal Dietz

• David Valle

• Victor McKusick

Managing Beatrice

Monitor her vasculature

Continue losartan

Further the investigation

Find other Beatrices

The Ultimate Charmer