PMID- 10053005
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 64
IP  - 3
DP  - 1999 Mar
TI  - Characterization and mutation analysis of human LEFTY A and LEFTY B, homologues
      of murine genes implicated in left-right axis development.
PG  - 712-21
AB  - Members of the transforming growth factor (TGF)-beta family of cell-signaling
      molecules have been implicated recently in mammalian left-right (LR) axis
      development, the process by which vertebrates lateralize unpaired organs (e.g.,
      heart, stomach, and spleen). Two family members, Lefty1 and Lefty2, are expressed
      exclusively on the left side of the mouse embryo by 8.0 days post coitum. This
      asymmetry is lost or reversed in two murine models of abnormal LR-axis
      specification, inversus viscerum (iv) and inversion of embryonic turning (inv).
      Furthermore, mice homozygous for a Lefty1 null allele manifest LR malformations
      and misexpress Lefty2. We hypothesized that Lefty mutations may be associated
      with human LR-axis malformations. We now report characterization of two Lefty
      homologues, LEFTY A and LEFTY B, separated by approximately 50 kb on chromosome
      1q42. Each comprises four exons spliced at identical positions. LEFTY A is
      identical to ebaf, a cDNA previously identified in a search for genes expressed
      in human endometrium. The deduced amino acid sequences of LEFTY A and LEFTY B are
      more similar to each other than to Lefty1 or Lefty2. Analysis of 126 human cases 
      of LR-axis malformations showed one nonsense and one missense mutation in LEFTY
      A. Both mutations lie in the cysteine-knot region of the protein LEFTY A, and the
      phenotype of affected individuals is very similar to that typically seen in
      Lefty1-/- mice with LR-axis malformations.
FAU - Kosaki, K
AU  - Kosaki K
AD  - Department of Pathology S230, Baylor College of Medicine, Houston, TX 77030, USA.
FAU - Bassi, M T
AU  - Bassi MT
FAU - Kosaki, R
AU  - Kosaki R
FAU - Lewin, M
AU  - Lewin M
FAU - Belmont, J
AU  - Belmont J
FAU - Schauer, G
AU  - Schauer G
FAU - Casey, B
AU  - Casey B
LA  - eng
GR  - HD01078/HD/NICHD NIH HHS/United States
GR  - HD36003/HD/NICHD NIH HHS/United States
GR  - P30 HD24064/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (LEFTY1 protein, human)
RN  - 0 (Left-Right Determination Factors)
RN  - 0 (Lefty2 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Body Patterning/*genetics
MH  - Chromosomes, Human, Pair 1
MH  - Exons
MH  - Genomic Library
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Introns
MH  - Left-Right Determination Factors
MH  - Mice
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Phenotype
MH  - Placenta/metabolism
MH  - Polymorphism, Single-Stranded Conformational
MH  - Restriction Mapping
MH  - Sequence Homology, Amino Acid
MH  - Transforming Growth Factor beta/*genetics
PMC - PMC1377788
EDAT- 1999/03/03 03:04
MHDA- 2000/03/21 09:00
CRDT- 1999/03/03 03:04
PHST- 1999/03/03 03:04 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/03/03 03:04 [entrez]
AID - S0002-9297(07)61708-X [pii]
AID - 10.1086/302289 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Mar;64(3):712-21. doi: 10.1086/302289.