title: Congenital arhinia: molecular-genetic analysis of five patients.
abstract: Congenital arhinia, complete absence of the nose, is an extremely rare anomaly with unknown cause. To our knowledge, a total of 36 cases have been reported, but there has been no molecular-genetic study on this anomaly. We encountered a sporadic case of congenital arhinia associated with a de novo chromosomal translocation, t(3;12)(q13.2;p11.2). This led us to analyze the patient by BAC-based FISH for translocation breakpoints and whole-genome array CGH for other possible deletions/duplications in the genome. We found in this patient an approximately 19 Mb deletion spanning from 3q11.2 to 3q13.31 but no disruption of any gene(s) at the other breakpoint, 12p11.2. As the deleted segment at 3q was a strong candidate region containing the putative arhinia gene, we also performed the array CGH in four other arhinia patients with normal karyotypes, as well as mutation analysis of two genes, COL8A1 and CPOX, selected among hundreds of genes located to the deleted region, because they are expressed during early stages of human craniofacial development. However, in the four patients, there were no copy number aberrations in the region examined or no mutations in the two genes. Although our study failed to identify the putative arhinia gene, the data may become a clue to unravel the underlying mechanism of arhinia.
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
authors.forename: Osamu
authors.initials: O
authors.lastname: Shimokawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Harada
authors.forename: Oystein E
authors.initials: OE
authors.lastname: Olsen
authors.forename: Jia-Woei
authors.initials: JW
authors.lastname: Hou
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Muhlbauer
authors.forename: Ellen
authors.initials: E
authors.lastname: Blinkenberg
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Kondo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kishino
authors.forename: Nobutomo
authors.initials: N
authors.lastname: Miwa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.forename: Norio
authors.initials: N
authors.lastname: Niikawa
authors.forename: Koh-Ichiro
authors.initials: K
authors.lastname: Yoshiura
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12; D002893:Chromosomes, Human, Pair 3; D024102:Collagen Type VIII / Q000235:genetics; D003304:Coproporphyrinogen Oxidase / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D009666:Nose / Q000002:abnormalities*; D009693:Nucleic Acid Hybridization / Q000379:methods; D020161:Physical Chromosome Mapping
chemical_list: D024102:Collagen Type VIII; D003304:Coproporphyrinogen Oxidase