PMID- 14755461
OWN - NLM
STAT- MEDLINE
DCOM- 20040728
LR  - 20200930
IS  - 1552-4825 (Print)
IS  - 1552-4825 (Linking)
VI  - 125A
IP  - 1
DP  - 2004 Feb 15
TI  - Targeted scan of fifteen regions for nonsyndromic cleft lip and palate in 
      Filipino families.
PG  - 17-22
AB  - Cleft lip with or without cleft palate (CL/P) is a congenital anomaly with 
      variable birth prevalence based on geographic origins, with the highest rates 
      commonly found in Asian populations. About 70% of cases are nonsyndromic (NS), in 
      which the affected individual has no other abnormalities. NS CL/P is a complex 
      disorder with genetic and environmental effects and no specific genetic loci yet 
      confirmed. Fifteen candidate regions were examined for linkage to NS CL/P. 
      Regions were chosen based on previous suggestive linkage and/or association in 
      human families, or suggestive animal model data. Polymorphic markers in these 
      regions were genotyped for analysis on 36 Filipino families comprised of 126 
      affected and 218 unaffected individuals. An additional 70 families with 149 
      affecteds were used for replication of suggestive results. Parametric (LOD score) 
      and nonparametric (SIMIBD) linkage analyses were performed as well as 
      transmission disequilibrium test (TDT) analysis. Five markers yielded suggestive 
      results from the 36 families. The parametric LOD scores for the MSX1-CA and 
      D4S1629 were >1.0 and the SIMIBD P values for D6S1029 and RFC1 are suggestive 
      (<0.06), while the SIMIBD P value of 0.01 for TGFA was significant. Since the 
      Msx1 mouse knockout has cleft palate and MSX1 mutations have been found in rare 
      cases of syndromic CL/P, this locus is especially plausible for linkage. Previous 
      studies have also found linkage of NS CL/P to 4q31 and 6p23. These regions 
      contain several candidate genes, including AP2 at 6p23 and FGF2, BMPR1B, and 
      MADH1 at 4q31. TGFA has both linkage and linkage disequilibrium data supporting 
      it as a candidate gene for NS CL/P. While no region was definitively confirmed 
      for linkage to NS CL/P, the data do support further investigation using larger 
      sample sizes and candidate gene studies at 2p13.2, 4p16.2, 4q31, 6p23, and 
      16q22-24.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Schultz, R E
AU  - Schultz RE
AD  - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA.
FAU - Cooper, M E
AU  - Cooper ME
FAU - Daack-Hirsch, S
AU  - Daack-Hirsch S
FAU - Shi, M
AU  - Shi M
FAU - Nepomucena, B
AU  - Nepomucena B
FAU - Graf, K A
AU  - Graf KA
FAU - O'Brien, E K
AU  - O'Brien EK
FAU - O'Brien, S E
AU  - O'Brien SE
FAU - Marazita, M L
AU  - Marazita ML
FAU - Murray, J C
AU  - Murray JC
LA  - eng
GR  - R01 DE016148/DE/NIDCR NIH HHS/United States
GR  - DE-08559/DE/NIDCR NIH HHS/United States
GR  - P60 DE13076/DE/NIDCR NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
SB  - IM
MH  - Chromosome Mapping/methods
MH  - Cleft Lip/*genetics/pathology
MH  - Cleft Palate/*genetics/pathology
MH  - Family Health
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Lod Score
MH  - Male
MH  - Microsatellite Repeats
MH  - Pedigree
MH  - Philippines
EDAT- 2004/02/03 05:00
MHDA- 2004/07/29 05:00
CRDT- 2004/02/03 05:00
PHST- 2004/02/03 05:00 [pubmed]
PHST- 2004/07/29 05:00 [medline]
PHST- 2004/02/03 05:00 [entrez]
AID - 10.1002/ajmg.a.20424 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2004 Feb 15;125A(1):17-22. doi: 10.1002/ajmg.a.20424.