Publication
Expanding the Genetic Spectrum of ANOS1 Mutations in Patients with Congenital Hypogonadotropic Hypogonadism
| dc.contributor.author | Gonçalves, CI | |
| dc.contributor.author | Fonseca, F | |
| dc.contributor.author | Borges, T | |
| dc.contributor.author | Cunha, F | |
| dc.contributor.author | Lemos, MC | |
| dc.date.accessioned | 2017-06-12T14:34:09Z | |
| dc.date.available | 2017-06-12T14:34:09Z | |
| dc.date.issued | 2017-03-01 | |
| dc.description.abstract | STUDY QUESTION: What is the prevalence and functional consequence of ANOS1 (KAL1) mutations in a group of men with congenital hypogonadotropic hypogonadism (CHH)? SUMMARY ANSWER: Three of forty-two (7.1%) patients presented ANOS1 mutations, including a novel splice site mutation leading to exon skipping and a novel contiguous gene deletion associated with ichthyosis. WHAT IS KNOWN ALREADY: CHH is characterized by lack of pubertal development and infertility, due to deficient production, secretion or action of GnRH, and can be associated with anosmia/hyposmia (Kallmann syndrome, KS) or with a normal sense of smell (normosmic CHH). Mutations in the anosmin-1 (ANOS1) gene are responsible for the X-linked recessive form of KS. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 42 unrelated men with CHH (20 with KS and 22 with normosmic CHH). PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were screened for mutations in the ANOS1 gene by DNA sequencing. Identified mutations were further investigated by RT-PCR analysis and multiplex ligation-dependent probe amplification (MLPA) analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Hemizygous mutations were identified in three (7.1%) KS cases: a novel splice acceptor site mutation (c.542-1G>C), leading to skipping of exon 5 in the ANOS1 transcript in a patient with self-reported normosmia (but hyposmic upon testing); a recurrent nonsense mutation (c.571C>T, p.Arg191*); and a novel 4.8 Mb deletion involving ANOS1 and eight other genes (VCX3B, VCX2, PNPLA4, VCX, STS, HDHD1, VCX3A and NLGN4X) in KS associated with ichthyosis. LIMITATIONS, REASONS FOR CAUTION: Objective olfactory testing was not performed in all cases of self-reported normosmia and this may have underestimated the olfactory deficits. WIDER IMPLICATIONS OF THE FINDINGS: This study further expands the spectrum of known genetic defects associated with CHH and suggests that patients with self-reported normal olfactory function should not be excluded from ANOS1 genetic testing. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Portuguese Foundation for Science and Technology. The authors have no conflicts of interest. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Hum Reprod. 2017 Mar 1;32(3):704-711. | pt_PT |
| dc.identifier.doi | 10.1093/humrep/dew354 | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.17/2711 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Oxford University Press | pt_PT |
| dc.subject | HCC END | pt_PT |
| dc.subject | Alleles | pt_PT |
| dc.subject | Cross-Sectional Studies | pt_PT |
| dc.subject | DNA Mutational Analysis | pt_PT |
| dc.subject | Exons | pt_PT |
| dc.subject | Extracellular Matrix Proteins/genetics | pt_PT |
| dc.subject | Gene Frequency | |
| dc.subject | Hypogonadism/congenital | |
| dc.subject | Hypogonadism/genetics | |
| dc.subject | Kallmann Syndrome/genetics | |
| dc.subject | Mutation | |
| dc.subject | Nerve Tissue Proteins/genetics | |
| dc.subject | Pedigree | |
| dc.title | Expanding the Genetic Spectrum of ANOS1 Mutations in Patients with Congenital Hypogonadotropic Hypogonadism | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 711 | pt_PT |
| oaire.citation.issue | 3 | pt_PT |
| oaire.citation.startPage | 704 | pt_PT |
| oaire.citation.title | Human Reproduction | pt_PT |
| oaire.citation.volume | 32 | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |