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.

A Genomewide Linkage Scan for Quantitative Trait Loci Influencing the Craniofacial Complex in Baboons (Papio hamadryas spp.)

“…For instance, the SIX3 gene found on HSA2p21, and linked to the posterior condylion measure in baboons, has been identified as a causative factor in holoprosencephaly, a disorder with severe craniofacial dysmorphology including cyclopia and a midline proboscis situated above the eye (Wallis et al 1999). Sato et al (2007) identified a patient with a deletion spanning HSA3q11.2, linked to the trait GoGn-S in our study, that presented with the rare condition of congenital arhinia (complete absence of the nose). Additionally, deletions in the HSA17p12 region, linked to N-Pr in this study, have been implicated in cleft palate associated with Smith-Magenis syndrome (Andrieux et al 2007).…”

Antenatal Diagnosis of Isolated Total Arhinia in the Second Trimester of Pregnancy

“…The chromosomal analysis in patients with arhinia showed normal results, excepting for 3 cases that had an abnormal karyotype: mos46, XX/47, XX, +9 [7]; 46, XY, inv(9) [8]; 46, XX, t(3;12) (q13.2; p11.2) (de novo) [9]. The third patient was also discovered to be the carrier of a 19 Mb deletion spanning from 3q11.2 to 3q13.31 at the 3q breakpoint of the translocation [10]. As the deleted segment at 3q was a strong candidate region for a putative arhinia gene, array CGH was performed in other arhinia patients, as well as mutation analysis of candidate genes [10].…”

“…The third patient was also discovered to be the carrier of a 19 Mb deletion spanning from 3q11.2 to 3q13.31 at the 3q breakpoint of the translocation [10]. As the deleted segment at 3q was a strong candidate region for a putative arhinia gene, array CGH was performed in other arhinia patients, as well as mutation analysis of candidate genes [10]. No consistent gene mutations have been discovered so far; therefore, genetic testing for a putative arhinia gene is not yet available.…”

Bosma arrhinia microphthalmia syndrome in a Mexican patient with a molecular analysis of PAX6

“…Indeed, it is unclear as to whether BAMS is genetically heterogeneous. This lack of information makes it difficult to establish an estimated frequency for BAMS, but 14 patients have been described in the literature (Table 1), making this the 15th reported case and the first reported case in a Mexican patient (Bosma et al, 1981;Thiele et al, 1996;Graham and Lee, 2006;Akkuzu et al, 2007;Sato et al, 2007;Tryggestad et al, 2013).…”

“…There have been only 37 reported cases of arrhinia (Olsen et al, 2001;Sato et al, 2007;Goyal et al, 2008). The spectrum of clinical manifestations with arrhinia includes midline defects and involves palatal, ocular, facial, and ear abnormalities.…”