Title
Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region
UMMS Affiliation
Department of Pediatrics
Publication Date
2007-02-16
Document Type
Article
Subjects
Abnormalities, Multiple; Child, Preschool; DNA Mutational Analysis; Female; Genotype; Humans; Infant; Infant, Newborn; Male; Middle Aged; *Mutation; Pedigree; Phenotype; Syndrome; Transcription Factors
Disciplines
Genetics and Genomics | Medical Genetics | Pediatrics
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.
DOI of Published Version
10.1002/humu.9476
Source
Hum Mutat. 2007 Feb;28(2):204-5. Link to article on publisher's site
Journal/Book/Conference Title
Human mutation
Related Resources
PubMed ID
17221874
Repository Citation
Botzenhart EM, Bartalini G, Blair E, Brady AF, Elmslie F, Chong KL, Christy K, Torres-Martinez W, Danesino C, Deardorff MA, Fryns J, 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. Genetics. https://doi.org/10.1002/humu.9476. Retrieved from https://escholarship.umassmed.edu/peds_genetics/13