Familial spherophakia with short stature caused by a novel homozygousADAMTS17mutation

Abstract

Recessive ADAMTS17 mutations are a recurrent cause of isolated spherophakia with short stature. In Saudi Arabia this phenotype shows allelic heterogeneity rather than founder effect.

Copy number variants in patients with short stature

“…GH secretion and circulating IGF-I were normal, but IGFBP-3 was low ( À2 SDS). Several arguments are in favor of a role of ADAMTS17 in growth regulation (for summary, see Table 3), including: (1) significant association with height in population GWAS; 1 (2) a short child with a similar terminal deletion in the DECIPHER database; (3) significant association with size in a GWAS in the domestic dog; 29 (4) human mutations in ADAMTS17 causing the acromelic chondrodysplasia Weill-Marchesani-like syndrome (OMIM #277600 and #608328); [30][31][32][33] and (5) association of members of the ADAMTSL/ADAMTS family with the modulation of fibrillin-1 function. 31,33 Unfortunately, expression of the rodent homolog of ADAMTS17 could not be investigated, because the gene was not represented on the microarrays used.…”

“…39 Case II.17, described previously, 12 carries a duplication of 3p12.3 containing part of ROBO2, encoding a receptor for SLIT2 and probably SLIT1, thought to function in axon guidance and cell migration. 40 Case II.21, born SGA, length À3.7 SDS and head circumference À3.1 SDS presented with clinodactily, a protruded [30][31][32][33] Associated with fibrillin-1 function. 31,33 Aldh1a3 and Lrrk1 higher expressed in murine GP; Chsy1 highly expressed in HZ and downregulated with age.…”

Molecular pathogenesis and management strategies of ectopia lentis

“…The only further report to date of a mutation in this gene causing this condition was later published by the same group in 2012. 50 Finally, mutations in LTBP2 on 14q24.3 have been described to cause EL, both in the context of WMS 51 and isolated with other ocular features. 52 Unlike other members of its protein family, LTBP2 does not bind to latent transforming growth factor, and instead its C-terminus has high affinity for the N-terminus of fibrillin-1.…”

Genetics of Canine Primary Glaucomas

“…[78][79][80][81][82][83][84] In contrast to ADAMTS17-mutant human patients with short stature and ocular signs, such as ectopia lentis/ PLL and glaucoma, 80,182,183 the canine disease phenotype is limited to ocular symptoms. 80 …”