PMID- 10533063
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20061115
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 14
IP  - 5
DP  - 1999
TI  - Townes-Brocks syndrome: detection of a SALL1 mutation hot spot and evidence for a
      position effect in one patient.
PG  - 377-86
AB  - Townes-Brocks syndrome (TBS) is an autosomal dominant developmental disorder
      characterized by anal and thumb malformations and by ear anomalies that can
      affect the three compartments and usually lead to hearing loss. The gene
      underlying TBS, SALL1, is a human homolog of the Drosophila spalt gene which
      encodes a transcription factor. A search for SALL1 mutations undertaken in 11
      unrelated affected individuals (five familial and six sporadic cases) led to the 
      detection of mutations in nine of them. One nonsense and six different novel
      frameshift mutations, all located in the second exon, were identified. Together
      with the previously reported mutations [Kohlhase et al., 1999], they establish
      that TBS results from haploinsufficiency. The finding of de novo mutations in the
      sporadic cases is consistent with the proposed complete penetrance of the
      disease. Moreover, the occurrence of the same 826C>T transition in a CG dimer, in
      three sporadic cases from the present series and three sporadic cases from the
      other series [Kohlhase et al., 1999] (i.e., six of the eight mutations identified
      in sporadic cases), reveals the existence of a mutation hotspot. Six different
      SALL1 polymorphisms were identified in the course of the present study, three of 
      which are clustered in a particular region of the gene that encodes a stretch of 
      serine residues. Finally, the chromosome 16 breakpoint of a t(5;16)(p15.3;q12.1) 
      translocation carried by a TBS-affected individual was mapped at least 180 kb
      telomeric to SALL1, thus indicating that a position effect underlies the disease 
      in this individual.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - Marlin, S
AU  - Marlin S
AD  - Unite de Genetique des Deficits Sensoriels, Institut Pasteur, Paris, France.
FAU - Blanchard, S
AU  - Blanchard S
FAU - Slim, R
AU  - Slim R
FAU - Lacombe, D
AU  - Lacombe D
FAU - Denoyelle, F
AU  - Denoyelle F
FAU - Alessandri, J L
AU  - Alessandri JL
FAU - Calzolari, E
AU  - Calzolari E
FAU - Drouin-Garraud, V
AU  - Drouin-Garraud V
FAU - Ferraz, F G
AU  - Ferraz FG
FAU - Fourmaintraux, A
AU  - Fourmaintraux A
FAU - Philip, N
AU  - Philip N
FAU - Toublanc, J E
AU  - Toublanc JE
FAU - Petit, C
AU  - Petit C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Codon, Nonsense)
RN  - 0 (DNA Primers)
RN  - 0 (SALL1 protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Abnormalities, Multiple/*genetics
MH  - Animals
MH  - Anus, Imperforate/*genetics
MH  - Base Sequence
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 16/genetics
MH  - Codon, Nonsense
MH  - DNA Primers/genetics
MH  - Ear, External/*abnormalities
MH  - Female
MH  - Frameshift Mutation
MH  - Hearing Loss, Sensorineural/*genetics
MH  - Humans
MH  - Male
MH  - *Mutation
MH  - Pedigree
MH  - Syndrome
MH  - Thumb/*abnormalities
MH  - Transcription Factors/*genetics
MH  - Translocation, Genetic
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1002/(SICI)1098-1004(199911)14:5<377::AID-HUMU3>3.0.CO;2-A [pii]
AID - 10.1002/(SICI)1098-1004(199911)14:5<377::AID-HUMU3>3.0.CO;2-A [doi]
PST - ppublish
SO  - Hum Mutat. 1999;14(5):377-86. doi:
      10.1002/(SICI)1098-1004(199911)14:5<377::AID-HUMU3>3.0.CO;2-A.