Autosomal dominant Stargardt-like macular dystrophy: Founder effect and reassessment of genetic heterogeneity

Larry A. Donoso, Arcilee T. Frost, Edwin M. Stone, Richard Weleber, Ian M. MacDonald, Gregory S. Hageman, Gerhard W. Cibis, Robert Ritter, Albert Edwards

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objectives: To characterize a disease-associated haplotype in 7 families with autosomal dominant Stargardt-like macular dystrophy and to determine whether these families share a common ancestor. Methods: Twenty-five polymorphic DNA markers spanning known dominant Stargardt-like gene loci were used to determine the haplotype associated with disease. In addition, an extensive genealogical investigation searching for a common ancestor shared by all of the 7 families was performed. Results: We clinically evaluated 171 patients and genotyped 145 samples. The same DNA haplotype on chromosome 6q16 was shared by all evaluated affected members within the 7 families. In addition, we were able to genealogically join all of the families into one larger family consisting of 31 branches and 2314 individuals. Twenty-seven branches have known living descendants, with 7 branches having affected family members. In addition, we refined the critical region for the gene to approximately 1000 kilobases (kb) and eliminated part or all of 9 candidate disease-causing genes. Conclusions: Our study indicates that most reported cases of autosomal dominant Stargardt-like macular dystrophy in North America are part of a single larger family associated with a gene locus on chromosome 6q16. Furthermore, the DNA haplotype associated with disease is useful in excluding individuals with phenotypically similar retinal conditions. Clinical Relevance: The disease-associated haplotype allows for more accurate genetic counseling to be given to individuals with a Stargardt-like phenotype inherited herited in an autosomal dominant pattern.

Original languageEnglish (US)
Pages (from-to)564-570
Number of pages7
JournalArchives of Ophthalmology
Volume119
Issue number4
StatePublished - 2001

Fingerprint

Founder Effect
Genetic Heterogeneity
Haplotypes
Genes
Chromosomes
Stargardt disease 3
DNA
Genetic Counseling
North America
Genetic Markers
Phenotype

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Donoso, L. A., Frost, A. T., Stone, E. M., Weleber, R., MacDonald, I. M., Hageman, G. S., ... Edwards, A. (2001). Autosomal dominant Stargardt-like macular dystrophy: Founder effect and reassessment of genetic heterogeneity. Archives of Ophthalmology, 119(4), 564-570.

Autosomal dominant Stargardt-like macular dystrophy : Founder effect and reassessment of genetic heterogeneity. / Donoso, Larry A.; Frost, Arcilee T.; Stone, Edwin M.; Weleber, Richard; MacDonald, Ian M.; Hageman, Gregory S.; Cibis, Gerhard W.; Ritter, Robert; Edwards, Albert.

In: Archives of Ophthalmology, Vol. 119, No. 4, 2001, p. 564-570.

Research output: Contribution to journalArticle

Donoso, LA, Frost, AT, Stone, EM, Weleber, R, MacDonald, IM, Hageman, GS, Cibis, GW, Ritter, R & Edwards, A 2001, 'Autosomal dominant Stargardt-like macular dystrophy: Founder effect and reassessment of genetic heterogeneity', Archives of Ophthalmology, vol. 119, no. 4, pp. 564-570.
Donoso, Larry A. ; Frost, Arcilee T. ; Stone, Edwin M. ; Weleber, Richard ; MacDonald, Ian M. ; Hageman, Gregory S. ; Cibis, Gerhard W. ; Ritter, Robert ; Edwards, Albert. / Autosomal dominant Stargardt-like macular dystrophy : Founder effect and reassessment of genetic heterogeneity. In: Archives of Ophthalmology. 2001 ; Vol. 119, No. 4. pp. 564-570.
@article{ff85cdaf31f84e96be3e204e9ab3e1ac,
title = "Autosomal dominant Stargardt-like macular dystrophy: Founder effect and reassessment of genetic heterogeneity",
abstract = "Objectives: To characterize a disease-associated haplotype in 7 families with autosomal dominant Stargardt-like macular dystrophy and to determine whether these families share a common ancestor. Methods: Twenty-five polymorphic DNA markers spanning known dominant Stargardt-like gene loci were used to determine the haplotype associated with disease. In addition, an extensive genealogical investigation searching for a common ancestor shared by all of the 7 families was performed. Results: We clinically evaluated 171 patients and genotyped 145 samples. The same DNA haplotype on chromosome 6q16 was shared by all evaluated affected members within the 7 families. In addition, we were able to genealogically join all of the families into one larger family consisting of 31 branches and 2314 individuals. Twenty-seven branches have known living descendants, with 7 branches having affected family members. In addition, we refined the critical region for the gene to approximately 1000 kilobases (kb) and eliminated part or all of 9 candidate disease-causing genes. Conclusions: Our study indicates that most reported cases of autosomal dominant Stargardt-like macular dystrophy in North America are part of a single larger family associated with a gene locus on chromosome 6q16. Furthermore, the DNA haplotype associated with disease is useful in excluding individuals with phenotypically similar retinal conditions. Clinical Relevance: The disease-associated haplotype allows for more accurate genetic counseling to be given to individuals with a Stargardt-like phenotype inherited herited in an autosomal dominant pattern.",
author = "Donoso, {Larry A.} and Frost, {Arcilee T.} and Stone, {Edwin M.} and Richard Weleber and MacDonald, {Ian M.} and Hageman, {Gregory S.} and Cibis, {Gerhard W.} and Robert Ritter and Albert Edwards",
year = "2001",
language = "English (US)",
volume = "119",
pages = "564--570",
journal = "JAMA Ophthalmology",
issn = "2168-6165",
publisher = "American Medical Association",
number = "4",

}

TY - JOUR

T1 - Autosomal dominant Stargardt-like macular dystrophy

T2 - Founder effect and reassessment of genetic heterogeneity

AU - Donoso, Larry A.

AU - Frost, Arcilee T.

AU - Stone, Edwin M.

AU - Weleber, Richard

AU - MacDonald, Ian M.

AU - Hageman, Gregory S.

AU - Cibis, Gerhard W.

AU - Ritter, Robert

AU - Edwards, Albert

PY - 2001

Y1 - 2001

N2 - Objectives: To characterize a disease-associated haplotype in 7 families with autosomal dominant Stargardt-like macular dystrophy and to determine whether these families share a common ancestor. Methods: Twenty-five polymorphic DNA markers spanning known dominant Stargardt-like gene loci were used to determine the haplotype associated with disease. In addition, an extensive genealogical investigation searching for a common ancestor shared by all of the 7 families was performed. Results: We clinically evaluated 171 patients and genotyped 145 samples. The same DNA haplotype on chromosome 6q16 was shared by all evaluated affected members within the 7 families. In addition, we were able to genealogically join all of the families into one larger family consisting of 31 branches and 2314 individuals. Twenty-seven branches have known living descendants, with 7 branches having affected family members. In addition, we refined the critical region for the gene to approximately 1000 kilobases (kb) and eliminated part or all of 9 candidate disease-causing genes. Conclusions: Our study indicates that most reported cases of autosomal dominant Stargardt-like macular dystrophy in North America are part of a single larger family associated with a gene locus on chromosome 6q16. Furthermore, the DNA haplotype associated with disease is useful in excluding individuals with phenotypically similar retinal conditions. Clinical Relevance: The disease-associated haplotype allows for more accurate genetic counseling to be given to individuals with a Stargardt-like phenotype inherited herited in an autosomal dominant pattern.

AB - Objectives: To characterize a disease-associated haplotype in 7 families with autosomal dominant Stargardt-like macular dystrophy and to determine whether these families share a common ancestor. Methods: Twenty-five polymorphic DNA markers spanning known dominant Stargardt-like gene loci were used to determine the haplotype associated with disease. In addition, an extensive genealogical investigation searching for a common ancestor shared by all of the 7 families was performed. Results: We clinically evaluated 171 patients and genotyped 145 samples. The same DNA haplotype on chromosome 6q16 was shared by all evaluated affected members within the 7 families. In addition, we were able to genealogically join all of the families into one larger family consisting of 31 branches and 2314 individuals. Twenty-seven branches have known living descendants, with 7 branches having affected family members. In addition, we refined the critical region for the gene to approximately 1000 kilobases (kb) and eliminated part or all of 9 candidate disease-causing genes. Conclusions: Our study indicates that most reported cases of autosomal dominant Stargardt-like macular dystrophy in North America are part of a single larger family associated with a gene locus on chromosome 6q16. Furthermore, the DNA haplotype associated with disease is useful in excluding individuals with phenotypically similar retinal conditions. Clinical Relevance: The disease-associated haplotype allows for more accurate genetic counseling to be given to individuals with a Stargardt-like phenotype inherited herited in an autosomal dominant pattern.

UR - http://www.scopus.com/inward/record.url?scp=0035069172&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035069172&partnerID=8YFLogxK

M3 - Article

C2 - 11296022

AN - SCOPUS:0035069172

VL - 119

SP - 564

EP - 570

JO - JAMA Ophthalmology

JF - JAMA Ophthalmology

SN - 2168-6165

IS - 4

ER -