title: Identification and characterization of KLHL4, a novel human homologue of the Drosophila Kelch gene that maps within the X-linked cleft palate and Ankyloglossia (CPX) critical region.
abstract: X-linked cleft palate (CPX) is a rare nonsyndromic form of orofacial clefting that is, unlike more common forms, inherited as a highly penetrant Mendelian trait. Linkage studies using a large Icelandic kindred localized the gene to Xq21.3, and a physical map defining a 2.0-Mb candidate region was subsequently constructed. Genomic sequence is now available for much of the critical region and has been surveyed for potential transcriptional units. Through this analysis, we have identified a novel human homologue of Kelch, KLHL4. The transcript represents a mRNA of approximately 3.6 kb and encodes a protein of 718 amino acids. Protein domain analysis reveals six tandem repeats (Kelch repeats) at the C-terminus and a POZ/BTB protein-binding domain toward the N-terminus, characteristic of Drosophila Kelch and other family members. KLHL4 consists of 11 exons spanning a genomic interval of approximately 150 kb. From EST sequences and RT-PCR analysis, there is evidence for the use of alternative 3' UTRs. The mRNA is expressed in a range of fetal tissues including tongue, palate, and mandible. Mutational analysis in affected CPX patients revealed one sequence alteration that was most likely to be a silent polymorphism.
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College, Hammersmith Campus, Du Cane Road, London, W12 ONN, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Braybrook
authors.forename: G
authors.initials: G
authors.lastname: Warry
authors.forename: G
authors.initials: G
authors.lastname: Howell
authors.forename: A
authors.initials: A
authors.lastname: Arnason
authors.forename: A
authors.initials: A
authors.lastname: Bjornsson
authors.forename: G E
authors.initials: GE
authors.lastname: Moore
authors.forename: M T
authors.initials: MT
authors.lastname: Ross
authors.forename: P
authors.initials: P
authors.lastname: Stanier
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002972:Cleft Palate / Q000235:genetics*; D003598:Cytoskeletal Proteins; D004330:Drosophila; D029721:Drosophila Proteins; D005091:Exons; D005260:Female; D005333:Fetus / Q000378:metabolism; D015870:Gene Expression; D008040:Genetic Linkage; D005820:Genetic Testing; D006801:Humans; D007438:Introns; D008297:Male; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D014960:X Chromosome
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; C430095:KLHL4 protein, human; D008840:Microfilament Proteins; C080353:kel protein, Drosophila