Abstract
Ectopia lentis is a genetically heterogeneous condition that is characterized by the subluxation of the lens resulting from the disruption of the zonular fibers. Patients with ectopia lentis commonly present with a marked loss in visual acuity in addition to a number of possibly accompanying ocular complications including cataract, myopia, and retinal detachment. We here describe an isolated form of ectopia lentis in a large inbred family that shows autosomal-recessive inheritance. We map the ectopia lentis locus in this family to the pericentromeric region on chromosome 1 (1p13.2-q21.1). The linkage region contains well more than 60 genes. Mutation screening of four candidate genes revealed a homozygous nonsense mutation in exon 11 of ADAMTSL4 (p.Y595X; c.1785T→G) in all affected individuals that is absent in 380 control chromosomes. The mutation would result in a truncated protein of half the original length, if the mRNA escapes nonsense-mediated decay.We conclude that mutations in ADAMTSL4 are responsible for autosomal-recessive simple ectopia lentis and that ADAMTS-like4 plays a role in the development and/or integrity of the zonular fibers.
| Original language | English |
|---|---|
| Pages (from-to) | 274-278 |
| Number of pages | 5 |
| Journal | American Journal of Human Genetics |
| Volume | 84 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 8 Aug 2008 |
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ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
A homozygous mutation in ADAMTSL4 causes autosomal-recessive isolated ectopia lentis. / Ahram, Dina; Sato, T. Shawn; Kohilan, Abdulghni; Tayeh, Marwan; Chen, Shan; Leal, Suzanne; Al-Salem, Mahmoud; El-Shanti, Hatem.
In: American Journal of Human Genetics, Vol. 84, No. 2, 08.08.2008, p. 274-278.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A homozygous mutation in ADAMTSL4 causes autosomal-recessive isolated ectopia lentis
AU - Ahram, Dina
AU - Sato, T. Shawn
AU - Kohilan, Abdulghni
AU - Tayeh, Marwan
AU - Chen, Shan
AU - Leal, Suzanne
AU - Al-Salem, Mahmoud
AU - El-Shanti, Hatem
PY - 2008/8/8
Y1 - 2008/8/8
N2 - Ectopia lentis is a genetically heterogeneous condition that is characterized by the subluxation of the lens resulting from the disruption of the zonular fibers. Patients with ectopia lentis commonly present with a marked loss in visual acuity in addition to a number of possibly accompanying ocular complications including cataract, myopia, and retinal detachment. We here describe an isolated form of ectopia lentis in a large inbred family that shows autosomal-recessive inheritance. We map the ectopia lentis locus in this family to the pericentromeric region on chromosome 1 (1p13.2-q21.1). The linkage region contains well more than 60 genes. Mutation screening of four candidate genes revealed a homozygous nonsense mutation in exon 11 of ADAMTSL4 (p.Y595X; c.1785T→G) in all affected individuals that is absent in 380 control chromosomes. The mutation would result in a truncated protein of half the original length, if the mRNA escapes nonsense-mediated decay.We conclude that mutations in ADAMTSL4 are responsible for autosomal-recessive simple ectopia lentis and that ADAMTS-like4 plays a role in the development and/or integrity of the zonular fibers.
AB - Ectopia lentis is a genetically heterogeneous condition that is characterized by the subluxation of the lens resulting from the disruption of the zonular fibers. Patients with ectopia lentis commonly present with a marked loss in visual acuity in addition to a number of possibly accompanying ocular complications including cataract, myopia, and retinal detachment. We here describe an isolated form of ectopia lentis in a large inbred family that shows autosomal-recessive inheritance. We map the ectopia lentis locus in this family to the pericentromeric region on chromosome 1 (1p13.2-q21.1). The linkage region contains well more than 60 genes. Mutation screening of four candidate genes revealed a homozygous nonsense mutation in exon 11 of ADAMTSL4 (p.Y595X; c.1785T→G) in all affected individuals that is absent in 380 control chromosomes. The mutation would result in a truncated protein of half the original length, if the mRNA escapes nonsense-mediated decay.We conclude that mutations in ADAMTSL4 are responsible for autosomal-recessive simple ectopia lentis and that ADAMTS-like4 plays a role in the development and/or integrity of the zonular fibers.
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U2 - 10.1016/j.ajhg.2009.01.007
DO - 10.1016/j.ajhg.2009.01.007
M3 - Article
VL - 84
SP - 274
EP - 278
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 2
ER -