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FREM1 mutations cause bifid nose, renal agenesis, and anorectal malformations syndrome.
- Source :
-
American journal of human genetics [Am J Hum Genet] 2009 Sep; Vol. 85 (3), pp. 414-8. - Publication Year :
- 2009
-
Abstract
- An autosomal-recessive syndrome of bifid nose and anorectal and renal anomalies (BNAR) was previously reported in a consanguineous Egyptian sibship. Here, we report the results of linkage analysis, on this family and on two other families with a similar phenotype, which identified a shared region of homozygosity on chromosome 9p22.2-p23. Candidate-gene analysis revealed homozygous frameshift and missense mutations in FREM1, which encodes an extracellular matrix component of basement membranes. In situ hybridization experiments demonstrated gene expression of Frem1 in the midline of E11.5 mouse embryos, in agreement with the observed cleft nose phenotype of our patients. FREM1 is part of a ternary complex that includes FRAS1 and FREM2, and mutations of the latter two genes have been reported to cause Fraser syndrome in mice and humans. The phenotypic variability previously reported for different Frem1 mouse mutants suggests that the apparently distinct phenotype of BNAR in humans may represent a previously unrecognized variant of Fraser syndrome.
- Subjects :
- Amino Acid Sequence
Animals
Base Sequence
DNA Mutational Analysis
Extracellular Matrix Proteins chemistry
Extracellular Matrix Proteins metabolism
Gene Expression Regulation, Developmental
Mice
Molecular Sequence Data
Nasal Mucosa metabolism
Nose embryology
Syndrome
Abnormalities, Multiple genetics
Extracellular Matrix Proteins genetics
Mutation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6605
- Volume :
- 85
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 19732862
- Full Text :
- https://doi.org/10.1016/j.ajhg.2009.08.010