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

Elke M. Botzenhart, Gabriella Bartalini, Edward Blair, Angela F. Brady, Frances Elmslie, Karen L. Chong, Katie Christy, Wilfredo Torres-Martinez, Cesare Danesino, Matthew A. Deardorff, Jean Pierre Fryns, Sandrine Marlin, Sixto Garcia-Minaur, Yorck Hellenbroich, Beverly N. Hay, Maila Penttinen, Vandana Shashi, Paulien Terhal, Lionel Van Maldergem, Margo L. WhitefordElaine Zackai, Jürgen Kohlhase

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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. (c) 2006 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)204-205
Number of pages2
JournalHuman Mutation
Volume28
Issue number2
Publication statusPublished - Feb 2007

Fingerprint

Mutation
Glutamine
Ear
Eye Manifestations
Kidney
Nonsense Codon
Zinc Fingers
Thumb
Genetic Association Studies
Exons
Proteins
Hand
Townes-Brocks syndrome
Phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Botzenhart, E. M., Bartalini, G., Blair, E., Brady, A. F., Elmslie, F., Chong, K. L., ... Kohlhase, J. (2007). Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region. Human Mutation, 28(2), 204-205.

Townes-Brocks syndrome : twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region. / Botzenhart, Elke M.; Bartalini, Gabriella; Blair, Edward; Brady, Angela F.; Elmslie, Frances; Chong, Karen L.; Christy, Katie; Torres-Martinez, Wilfredo; Danesino, Cesare; Deardorff, Matthew A.; Fryns, Jean Pierre; Marlin, Sandrine; Garcia-Minaur, Sixto; Hellenbroich, Yorck; Hay, Beverly N.; Penttinen, Maila; Shashi, Vandana; Terhal, Paulien; Van Maldergem, Lionel; Whiteford, Margo L.; Zackai, Elaine; Kohlhase, Jürgen.

In: Human Mutation, Vol. 28, No. 2, 02.2007, p. 204-205.

Research output: Contribution to journalArticle

Botzenhart, EM, Bartalini, G, Blair, E, Brady, AF, Elmslie, F, Chong, KL, Christy, K, Torres-Martinez, W, Danesino, C, Deardorff, MA, Fryns, JP, Marlin, S, Garcia-Minaur, S, Hellenbroich, Y, Hay, BN, Penttinen, M, Shashi, V, Terhal, P, Van Maldergem, L, Whiteford, ML, Zackai, E & Kohlhase, J 2007, 'Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region.', Human Mutation, vol. 28, no. 2, pp. 204-205.
Botzenhart EM, Bartalini G, Blair E, Brady AF, Elmslie F, Chong KL et al. Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region. Human Mutation. 2007 Feb;28(2):204-205.
Botzenhart, Elke M. ; Bartalini, Gabriella ; Blair, Edward ; Brady, Angela F. ; Elmslie, Frances ; Chong, Karen L. ; Christy, Katie ; Torres-Martinez, Wilfredo ; Danesino, Cesare ; Deardorff, Matthew A. ; Fryns, Jean Pierre ; Marlin, Sandrine ; Garcia-Minaur, Sixto ; Hellenbroich, Yorck ; Hay, Beverly N. ; Penttinen, Maila ; Shashi, Vandana ; Terhal, Paulien ; Van Maldergem, Lionel ; Whiteford, Margo L. ; Zackai, Elaine ; Kohlhase, Jürgen. / Townes-Brocks syndrome : twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region. In: Human Mutation. 2007 ; Vol. 28, No. 2. pp. 204-205.
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AU - Bartalini, Gabriella

AU - Blair, Edward

AU - Brady, Angela F.

AU - Elmslie, Frances

AU - Chong, Karen L.

AU - Christy, Katie

AU - Torres-Martinez, Wilfredo

AU - Danesino, Cesare

AU - Deardorff, Matthew A.

AU - Fryns, Jean Pierre

AU - Marlin, Sandrine

AU - Garcia-Minaur, Sixto

AU - Hellenbroich, Yorck

AU - Hay, Beverly N.

AU - Penttinen, Maila

AU - Shashi, Vandana

AU - Terhal, Paulien

AU - Van Maldergem, Lionel

AU - Whiteford, Margo L.

AU - Zackai, Elaine

AU - Kohlhase, Jürgen

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