Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome.
Ulnar-mammary syndrome is a rare pleiotropic disorder affecting limb, apocrine gland, tooth and genital development. We demonstrate that mutations in human TBX3, a member of the T-box gene family, cause ulnar-mammary syndrome in two families. Each mutation (a single nucleotide deletion and a splice-site mutation) is predicted to cause haploinsufficiency of TBX3, implying that critical levels of this transcription factor are required for morphogenesis of several organs. Limb abnormalities of ulnar-mammary syndrome involve posterior elements. Mutations in TBX5, a related and linked gene, cause anterior limb abnormalities in Holt-Oram syndrome. We suggest that during the evolution of TBX3 and TBX5 from a common ancestral gene, each has acquired specific yet complementary roles in patterning the mammalian upper limb.
Bamshad
M
M
Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.
Lin
R C
RC
Law
D J
DJ
Watkins
W C
WC
Krakowiak
P A
PA
Moore
M E
ME
Franceschini
P
P
Lala
R
R
Holmes
L B
LB
Gebuhr
T C
TC
Bruneau
B G
BG
Schinzel
A
A
Seidman
J G
JG
Seidman
C E
CE
Jorde
L B
LB
D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D001050:Apocrine Glands / Q000002:abnormalities*; D001132:Arm / Q000002:abnormalities*; D001483:Base Sequence; D001940:Breast / Q000002:abnormalities; D002881:Chromosomes, Human, Pair 12; D004252:DNA Mutational Analysis; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005835:Genitalia / Q000002:abnormalities*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D013577:Syndrome; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; C106884:TBX3 protein, human; D014157:Transcription Factors