PMID- 10612508
OWN - NLM
STAT- MEDLINE
DCOM- 19991228
LR  - 20190627
IS  - 0002-9394 (Print)
IS  - 0002-9394 (Linking)
VI  - 128
IP  - 6
DP  - 1999 Dec
TI  - A novel mutation in the ABCR gene in four patients with autosomal recessive
      Stargardt disease.
PG  - 720-4
AB  - PURPOSE: To identify additional mutations in the ABCR gene and describe the
      clinical features of four affected siblings with autosomal recessive Stargardt
      disease. METHODS: A cohort of eight siblings was identified for study. Four of
      these individuals were diagnosed with Stargardt disease based on clinical
      evaluation and fluorescein angiography. Blood samples were obtained from seven of
      eight siblings, including all those affected. All 50 exons of the ABCR gene were 
      analyzed by single-stranded confirmation polymorphism analysis, followed by
      direct sequencing of observed variants, to identify mutations in the ABCR gene.
      RESULTS: We identified a previously unreported kindred of eight siblings, four of
      whom had mutations in both of their ABCR alleles. A previously described G-to-C
      transversion of nucleotide 2588, predicting a Gly863Ala amino acid substitution, 
      and a novel G-to-A transition of nucleotide 161, resulting in a Cys54Tyr
      substitution, were identified. These mutations co-segregated with the affected
      members of this family. Three of the siblings demonstrated clinical features
      characteristic of classic Stargardt disease, with bilateral regions of macular
      atrophy associated with yellow-white "flavimaculatus" flecks in the posterior
      pole at the level of the retinal pigment epithelium. The fourth affected sibling 
      showed features of early Stargardt disease, with a beaten-bronze appearance to
      both maculas, as well as perimacular flecks. In all four affected patients,
      fluorescein angiography showed a characteristic peripheral dark choroid.
      CONCLUSIONS: We have identified both a previously described and a novel mutation 
      in the ABCR gene in four patients with autosomal recessive Stargardt disease.
      In-depth knowledge of the ABCR mutation spectrum in patients with Stargardt
      disease will provide for more efficient screening and may provide potential
      therapies for Stargardt disease and other retinal diseases.
FAU - Zhang, K
AU  - Zhang K
AD  - Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore,
      Maryland, USA. zhangk@welchlink.welch.jhu.edu
FAU - Garibaldi, D C
AU  - Garibaldi DC
FAU - Kniazeva, M
AU  - Kniazeva M
FAU - Albini, T
AU  - Albini T
FAU - Chiang, M F
AU  - Chiang MF
FAU - Kerrigan, M
AU  - Kerrigan M
FAU - Sunness, J S
AU  - Sunness JS
FAU - Han, M
AU  - Han M
FAU - Allikmets, R
AU  - Allikmets R
LA  - eng
GR  - N01-CO-56000/CO/NCI NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Ophthalmol
JT  - American journal of ophthalmology
JID - 0370500
RN  - 0 (ABCA4 protein, human)
RN  - 0 (ATP-Binding Cassette Transporters)
SB  - IM
MH  - ATP-Binding Cassette Transporters/*genetics
MH  - Adult
MH  - Base Sequence
MH  - Cohort Studies
MH  - DNA Mutational Analysis
MH  - Eye Diseases, Hereditary/*genetics/pathology
MH  - Female
MH  - Fluorescein Angiography
MH  - Fundus Oculi
MH  - Humans
MH  - Macular Degeneration/*genetics/pathology
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Pedigree
MH  - *Point Mutation
MH  - Polymorphism, Single-Stranded Conformational
MH  - Sequence Analysis, DNA
MH  - Visual Acuity
EDAT- 1999/12/28 00:00
MHDA- 1999/12/28 00:01
CRDT- 1999/12/28 00:00
PHST- 1999/12/28 00:00 [pubmed]
PHST- 1999/12/28 00:01 [medline]
PHST- 1999/12/28 00:00 [entrez]
AID - S0002939499002366 [pii]
AID - 10.1016/s0002-9394(99)00236-6 [doi]
PST - ppublish
SO  - Am J Ophthalmol. 1999 Dec;128(6):720-4. doi: 10.1016/s0002-9394(99)00236-6.