View abstract

This abstract is assigned to session Poster session

Title	Best VMD & ARB in one sibship
Abstract Nr.	P127

Purpose	To describe a family in which both Best vitelliform macular dystrophy and autosomal recessive bestrophinopathy segregate.
Methods	A brother and sister and their parents underwent a full ophthalmological examination, including extensive specialised imaging and visual electrophysiology.
Results	BCVA in the 32-year old proband was 3/10 in the RE and 7/10 in the LE. Slit-lamp examination was unremarkable in BE. Fundoscopy, OCT and imaging showed an ARB phenotype with a bilateral shallow retinal detachment in the macula with scattered deposits in and around it, as well as superior and nasal to the optic disc. The EOG light rise was absent, whilst the ERG revealed a rod-cone dystrophy. The phenotype in his 24-year old sister was that of BVMD, with a BCVA of 10/10 in the RE and 6/10 in the LE. EOG showed an absent light rise, whereas the ERG was normal. Both parents were entirely normal. Molecular analysis of BEST1 revealed one known mutation in the proband: c.602 T>C (p.Ile201Thr). In addition, a rare silent variant/mutation was identified: c.624G>A (p.Gln208Gln), which has also been associated with BVMD. These mutations were in trans. The sister with BVMD is heterozygous for c.602 T>C. Segregation analysis revealed that the c.602 T>C BEST1 allele was inherited by both siblings from their unaffected father, whereas the c.624G>A allele was de novo in the proband.
Conclusion	Heterozygosity for the BEST1 c.602 T>C (p.Ile201Thr) mutation can underly BVMD, whereas in combination with c.624G>A (p.Gln208Gln) it can cause ARB. BVMD and ARB can segregate in the same family.

Authors 1

Last name	LEROY
Initials	BP
Department	Dept of Ophth & Ctr for Med Genet, Ghent Univ Hosp & Ghent Univ & CHOP
City	Ghent & Philadelphia

Authors 2

Last name	DE BAERE
Initials	E
Department	Ctr for Med Genet, Ghent Univ Hosp & Ghent Univ
City	Ghent