PMID- 10441331
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 9
DP  - 1999 Sep
TI  - Expression of the Sonic hedgehog (SHH ) gene during early human development and
      phenotypic expression of new mutations causing holoprosencephaly.
PG  - 1683-9
AB  - Holoprosencephaly (HPE), the most common developmental defect of the forebrain
      and the face, is genetically heterogeneous. One of the genes involved, Sonic
      hedgehog ( SHH ), on 7q36, has been identified as the first HPE-causing gene both
      in mouse and humans. In order to delineate the phenotype of specific SHH
      mutations, we described the expression of the SHH gene during early human
      embryogenesis and investigated the phenotype of novel SHH mutations. In situ
      hybridization studies were performed on paraffin-embedded human embryo sections
      at three different development stages. These studies show that SHH is expressed
      in the notochord, the floorplate, the brain, the zone of polarizing activity and 
      the gut. We also report on the phenotype of four novel mutations identified in 40
      HPE families (two in isolated HPE and two in familial HPE). Expressivity ranged
      from alobar HPE to microcephaly and hypoplasia of the pituitary gland in one
      family, and from HPE to an asymptomatic form in another family. No SHH mutation
      was found in six polymalformed cases combining HPE with other defects, such as
      skeletal, limb, cardiac, anal and/or renal anomalies. This study confirms the
      genetic heterogeneity of HPE, and further demonstrates that SHH mutations are
      associated with a broad spectrum of cerebral midline defects.
FAU - Odent, S
AU  - Odent S
AD  - Service de Genetique Clinique et Moleculaire, CHU Pontchaillou, rue Henri Le
      Guillou, 35033 Rennes Cedex 9, France. sylvie.odent@chu-rennes.fr
FAU - Atti-Bitach, T
AU  - Atti-Bitach T
FAU - Blayau, M
AU  - Blayau M
FAU - Mathieu, M
AU  - Mathieu M
FAU - Aug, J
AU  - Aug J
FAU - Delezo de, A L
AU  - Delezo de AL
FAU - Gall, J Y
AU  - Gall JY
FAU - Le Marec, B
AU  - Le Marec B
FAU - Munnich, A
AU  - Munnich A
FAU - David, V
AU  - David V
FAU - Vekemans, M
AU  - Vekemans M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Proteins)
RN  - 0 (SHH protein, human)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Brain/embryology
MH  - DNA Mutational Analysis
MH  - Embryonic and Fetal Development
MH  - Female
MH  - Gene Expression Regulation, Developmental/*genetics
MH  - Hedgehog Proteins
MH  - Holoprosencephaly/embryology/*genetics
MH  - Humans
MH  - In Situ Hybridization
MH  - Male
MH  - *Mutation
MH  - Pedigree
MH  - Phenotype
MH  - Proteins/*genetics
MH  - *Trans-Activators
EDAT- 1999/08/11 00:00
MHDA- 1999/08/11 00:01
CRDT- 1999/08/11 00:00
PHST- 1999/08/11 00:00 [pubmed]
PHST- 1999/08/11 00:01 [medline]
PHST- 1999/08/11 00:00 [entrez]
AID - ddc187 [pii]
AID - 10.1093/hmg/8.9.1683 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Sep;8(9):1683-9. doi: 10.1093/hmg/8.9.1683.