Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region.

Journal Article (Journal Article)

Townes-Brocks syndrome (TBS) is an autosomal dominant malformation syndrome characterized by renal, anal, ear, and thumb anomalies caused by SALL1 mutations. To date, 36 SALL1 mutations have been described in TBS patients. All but three of those, namely p.R276X, p.S372X, and c.1404dupG, have been found only in single families thereby preventing phenotype-genotype correlations. Here we present 20 novel mutations (12 short deletions, five short duplications, three nonsense mutations) in 20 unrelated families. We delineate the phenotypes and report previously unknown ocular manifestations, i.e. congenital cataracts with unilateral microphthalmia. We show that 46 out of the now 56 SALL1 mutations are located between the coding regions for the glutamine-rich domain mediating SALL protein interactions and 65 bp 3' of the coding region for the first double zinc finger domain, narrowing the SALL1 mutational hotspot region to a stretch of 802 bp within exon 2. Of note, only two SALL1 mutations would result in truncated proteins without the glutamine-rich domain, one of which is reported here. The latter is associated with anal, ear, hand, and renal manifestations, indicating that the glutamine-rich domain is not required for typical TBS.

Full Text

Duke Authors

Cited Authors

  • Botzenhart, EM; Bartalini, G; Blair, E; Brady, AF; Elmslie, F; Chong, KL; Christy, K; Torres-Martinez, W; Danesino, C; Deardorff, MA; Fryns, J-P; Marlin, S; Garcia-Minaur, S; Hellenbroich, Y; Hay, BN; Penttinen, M; Shashi, V; Terhal, P; Van Maldergem, L; Whiteford, ML; Zackai, E; Kohlhase, J

Published Date

  • February 2007

Published In

Volume / Issue

  • 28 / 2

Start / End Page

  • 204 - 205

PubMed ID

  • 17221874

Electronic International Standard Serial Number (EISSN)

  • 1098-1004

Digital Object Identifier (DOI)

  • 10.1002/humu.9476


  • eng

Conference Location

  • United States