PMID- 17201812
OWN - NLM
STAT- MEDLINE
DCOM- 20070723
LR  - 20220310
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 66
IP  - 1
DP  - 2007 Jan
TI  - SHOX mutations in idiopathic short stature and Leri-Weill dyschondrosteosis: 
      frequency and phenotypic variability.
PG  - 130-5
AB  - OBJECTIVE: The frequency of SHOX mutations in children with idiopathic short 
      stature (ISS) has been found to be variable. We analysed the SHOX gene in 
      children with ISS and Leri-Weill dyschondrosteosis (LWD) and evaluated the 
      phenotypic variability in patients harbouring SHOX mutations. PATIENTS: 
      Sixty-three ISS, nine LWD children and 21 affected relatives. METHODS: SHOX gene 
      deletion was evaluated by fluorescence in situ hybridization (FISH), Southern 
      blotting and segregation study of polymorphic marker. Point mutations were 
      assessed by direct DNA sequencing. RESULTS: None of the ISS patients presented 
      SHOX deletions, but two (3.2%) presented heterozygous point mutations, including 
      the novel R147H mutation. However, when ISS patients were selected by sitting 
      height : height ratio (SH/H) for age > 2 SD, mutation frequency detection 
      increased to 22%. Eight (89%) LWD patients had SHOX deletions, but none had point 
      mutations. Analysis of the other relatives in the families carrying SHOX 
      mutations identified 14 children and 17 adult patients. A broad phenotypic 
      variability was observed in all families regarding short stature severity and 
      Madelung deformities. However, the presence of disproportional height, assessed 
      by SH/H, was observed in all children and 82% of adult patients, being the most 
      common feature in our patients with SHOX mutations. CONCLUSION: Patients with 
      SHOX mutations present a broad phenotypic variability. SHOX mutations are very 
      frequent in LWD (89%), in opposition to ISS (3.2%) in our cohort. The use of SH/H 
      SDS as a selection criterion increases the frequency of SHOX mutation detection 
      to 22% and should be used for selecting ISS children to undergo SHOX mutation 
      molecular studies.
FAU - Jorge, Alexander A L
AU  - Jorge AA
AD  - Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica 
      Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas, SP, 
      Brazil. alexj@usp.br
FAU - Souza, Silvia C
AU  - Souza SC
FAU - Nishi, Miriam Y
AU  - Nishi MY
FAU - Billerbeck, Ana E
AU  - Billerbeck AE
FAU - Liborio, Debora C C
AU  - Liborio DC
FAU - Kim, Chong A
AU  - Kim CA
FAU - Arnhold, Ivo J P
AU  - Arnhold IJ
FAU - Mendonca, Berenice B
AU  - Mendonca BB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (Homeodomain Proteins)
RN  - 0 (SHOX protein, human)
RN  - 0 (Short Stature Homeobox Protein)
SB  - IM
MH  - Adult
MH  - Blotting, Southern
MH  - Case-Control Studies
MH  - Chi-Square Distribution
MH  - Child
MH  - Consensus Sequence
MH  - DNA Mutational Analysis
MH  - Female
MH  - Gene Frequency
MH  - *Genes, Homeobox
MH  - Growth Disorders/*genetics
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Osteochondrodysplasias/*genetics
MH  - Pedigree
MH  - Phenotype
MH  - *Point Mutation
MH  - Short Stature Homeobox Protein
EDAT- 2007/01/05 09:00
MHDA- 2007/07/24 09:00
CRDT- 2007/01/05 09:00
PHST- 2007/01/05 09:00 [pubmed]
PHST- 2007/07/24 09:00 [medline]
PHST- 2007/01/05 09:00 [entrez]
AID - CEN2698 [pii]
AID - 10.1111/j.1365-2265.2006.02698.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2007 Jan;66(1):130-5. doi: 
      10.1111/j.1365-2265.2006.02698.x.