PMID- 10521292
OWN - NLM
STAT- MEDLINE
DCOM- 19991210
LR  - 20220419
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 5
DP  - 1999 Nov
TI  - Mutation analysis of core binding factor A1 in patients with cleidocranial
      dysplasia.
PG  - 1268-78
AB  - Cleidocranial dysplasia (CCD) is a dominantly inherited disorder characterized by
      patent fontanelles, wide cranial sutures, hypoplasia of clavicles, short stature,
      supernumerary teeth, and other skeletal anomalies. We recently demonstrated that 
      mutations in the transcription factor CBFA1, on chromosome 6p21, are associated
      with CCD. We have now analyzed the CBFA1 gene in 42 unrelated patients with CCD. 
      In 18 patients, mutations were detected in the coding region of the CBFA1 gene,
      including 8 frameshift, 2 nonsense, and 9 missense mutations, as well as 2 novel 
      polymorphisms. A cluster of missense mutations at arginine 225 (R225) identifies 
      this residue as crucial for CBFA1 function. In vitro green fluorescent protein
      fusion studies show that R225 mutations interfere with nuclear accumulation of
      CBFA1 protein. There is no phenotypic difference between patients with deletions 
      or frameshifts and those with other intragenic mutations, suggesting that CCD is 
      generally caused by haploinsufficiency. However, we were able to extend the CCD
      phenotypic spectrum. A missense mutation identified in one family with
      supernumerary teeth and a radiologically normal skeleton indicates that mutations
      in CBFA1 can be associated exclusively with a dental phenotype. In addition, one 
      patient with severe CCD and a frameshift mutation in codon 402 had osteoporosis
      leading to recurrent bone fractures and scoliosis, providing first evidence that 
      CBFA1 may help maintain adult bone, in addition to its function in bone
      development.
FAU - Quack, I
AU  - Quack I
AD  - Department of Hematology, University of Freiburg Medical Center, Freiburg,
      Germany.
FAU - Vonderstrass, B
AU  - Vonderstrass B
FAU - Stock, M
AU  - Stock M
FAU - Aylsworth, A S
AU  - Aylsworth AS
FAU - Becker, A
AU  - Becker A
FAU - Brueton, L
AU  - Brueton L
FAU - Lee, P J
AU  - Lee PJ
FAU - Majewski, F
AU  - Majewski F
FAU - Mulliken, J B
AU  - Mulliken JB
FAU - Suri, M
AU  - Suri M
FAU - Zenker, M
AU  - Zenker M
FAU - Mundlos, S
AU  - Mundlos S
FAU - Otto, F
AU  - Otto F
LA  - eng
SI  - GENBANK/AF001443
SI  - GENBANK/AF001444
SI  - GENBANK/AF001445
SI  - GENBANK/AF001446
SI  - GENBANK/AF001447
SI  - GENBANK/AF001448
SI  - GENBANK/AF001449
SI  - GENBANK/AF001450
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Core Binding Factors)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Bone and Bones/diagnostic imaging/pathology
MH  - Cell Line
MH  - Cleidocranial Dysplasia/diagnostic imaging/*genetics
MH  - Core Binding Factor Alpha 1 Subunit
MH  - Core Binding Factors
MH  - DNA Mutational Analysis
MH  - Frameshift Mutation
MH  - Green Fluorescent Proteins
MH  - Humans
MH  - Luminescent Proteins
MH  - Microscopy, Fluorescence
MH  - Molecular Sequence Data
MH  - Mutation, Missense
MH  - *Neoplasm Proteins
MH  - Phenotype
MH  - Polymorphism, Genetic
MH  - Radiography
MH  - Recombinant Fusion Proteins
MH  - Sequence Deletion
MH  - Tooth/pathology
MH  - Transcription Factors/*genetics
MH  - Transfection
PMC - PMC1288279
EDAT- 1999/10/16 09:00
MHDA- 2000/03/21 09:00
CRDT- 1999/10/16 09:00
PHST- 1999/10/16 09:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/10/16 09:00 [entrez]
AID - S0002-9297(07)62133-8 [pii]
AID - 10.1086/302622 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Nov;65(5):1268-78. doi: 10.1086/302622.