PMID- 16799922
OWN - NLM
STAT- MEDLINE
DCOM- 20061016
LR  - 20191210
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 27
IP  - 8
DP  - 2006 Aug
TI  - Father-to-daughter transmission of Cornelia de Lange syndrome caused by a 
      mutation in the 5' untranslated region of the NIPBL Gene.
PG  - 731-5
AB  - Cornelia de Lange syndrome (CdLS; also called Brachmann de Lange syndrome) is a 
      developmental disorder characterized by typical facial dysmorphism, growth and 
      mental retardation, microcephaly, and various malformations. Mutations in the 
      NIPBL gene have been identified in approximately 40% of reported cases, 
      suggesting either genetic heterogeneity or that some NIPBL mutations are not 
      detected by current screening strategies. We screened a cohort of 21 patients 
      with no previously identified NIPBL anomaly for mutations in the 5' untranslated 
      region (5'UTR) and the proximal promoter of the NIPBL gene. We identified a 
      heterozygous deletion-insertion mutation in exon 1, 321 nucleotides upstream of 
      the translation initiation codon (c.-321_-320delCCinsA) in one affected girl and 
      her mildly affected father. This mutation altered highly conserved nucleotides, 
      was not found in 400 control alleles, arose de novo in the father, and 
      cosegregated with the disease in the family. Using real-time quantitative PCR, we 
      showed that NIPBL mRNA expression was lowered in patients' lymphocytes compared 
      to control samples. Finally, we showed that, when subcloned into a luciferase 
      reporter vector, the mutation leads to a significant reduction of reporter gene 
      activity. Our results demonstrate that mutations in the 5' noncoding region of 
      the NIPBL gene can be involved in the pathogenesis of CdLS. Mutations affecting 
      this region of the gene might be associated with a milder phenotype.
FAU - Borck, Guntram
AU  - Borck G
AD  - INSERM U781 and Departement de Genetique, Hopital Necker-Enfants Malades, Paris, 
      France. borck@necker.fr
FAU - Zarhrate, Mohamed
AU  - Zarhrate M
FAU - Cluzeau, Celine
AU  - Cluzeau C
FAU - Bal, Elodie
AU  - Bal E
FAU - Bonnefont, Jean-Paul
AU  - Bonnefont JP
FAU - Munnich, Arnold
AU  - Munnich A
FAU - Cormier-Daire, Valerie
AU  - Cormier-Daire V
FAU - Colleaux, Laurence
AU  - Colleaux L
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (NIPBL protein, human)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Adolescent
MH  - Cell Cycle Proteins
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - CpG Islands
MH  - De Lange Syndrome/*genetics
MH  - Female
MH  - Genes, Reporter
MH  - Genetic Heterogeneity
MH  - Genetic Testing
MH  - Humans
MH  - Infant
MH  - *Inheritance Patterns
MH  - Luciferases/analysis
MH  - Male
MH  - *Mutation
MH  - Pedigree
MH  - Promoter Regions, Genetic
MH  - Proteins/*genetics
MH  - RNA, Messenger/metabolism
EDAT- 2006/06/27 09:00
MHDA- 2006/10/17 09:00
CRDT- 2006/06/27 09:00
PHST- 2006/06/27 09:00 [pubmed]
PHST- 2006/10/17 09:00 [medline]
PHST- 2006/06/27 09:00 [entrez]
AID - 10.1002/humu.20380 [doi]
PST - ppublish
SO  - Hum Mutat. 2006 Aug;27(8):731-5. doi: 10.1002/humu.20380.