Homozygous mutations in ADAMTS10 and ADAMTS17 cause lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature.
Weill-Marchesani syndrome (WMS) is a well-characterized disorder in which patients develop eye and skeletal abnormalities. Autosomal-recessive and autosomal-dominant forms of WMS are caused by mutations in ADAMTS10 and FBN1 genes, respectively. Here we report on 13 patients from seven unrelated families from the Arabian Peninsula. These patients have a constellation of features that fall within the WMS spectrum and follow an autosomal-recessive mode of inheritance. Individuals who came from two families and met the diagnostic criteria for WMS were each found to have a different homozygous missense mutation in ADAMTS10. Linkage analysis and direct sequencing of candidate genes in another two families and a sporadic case with phenotypes best described as WMS-like led to the identification of three homozygous mutations in the closely related ADAMTS17 gene. Our clinical and genetic findings suggest that ADAMTS17 plays a role in crystalline lens zonules and connective tissue formation and that mutations in ADAMTS17 are sufficient to produce some of the main features typically described in WMS.
Morales
Jose
J
King Khaled Eye Specialist Hospital, and College of Medicine, King Saud University, Riyadh 11462, Saudi Arabia.
Al-Sharif
Latifa
L
Khalil
Dania S
DS
Shinwari
Jameela M A
JM
Bavi
Prashant
P
Al-Mahrouqi
Rahima A
RA
Al-Rajhi
Ali
A
Alkuraya
Fowzan S
FS
Meyer
Brian F
BF
Al Tassan
Nada
N
D051722:ADAM Proteins / Q000235:genetics*; D000071096:ADAMTS Proteins; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004392:Dwarfism / Q000235:genetics*; D004479:Ectopia Lentis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005808:Genes, Recessive; D008040:Genetic Linkage; D005901:Glaucoma / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009216:Myopia / Q000235:genetics*; D009679:Nuclear Family; D010375:Pedigree; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA
D020033:Protein Isoforms; D004247:DNA; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C494614:ADAMTS10 protein, human