Mutation spectrum and frequency of copy number variations of the ANOS1 gene in patients with Kallmann syndrome or normosmic isolated hypogonadotropic hypogonadism
Objective: This study was performed to investigate the molecular characteristics and frequency of copy number variations (CNVs) of ANOS1 in patients with Kallmann syndrome (KS) or normosmic isolated hypogonadotropic hypogonadism (nIHH) using multiplex ligation-dependent probe amplification (MLPA) an...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2023-04-01
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| Series: | Endocrine Connections |
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| Online Access: | https://ec.bioscientifica.com/view/journals/ec/12/5/EC-22-0413.xml |
| _version_ | 1827963057819615232 |
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| author | Ja Hye Kim Yunha Choi Soojin Hwang Ji-Hee Yoon Jieun Lee Min Jae Kang Gu-Hwan Kim Han-Wook Yoo Jin-Ho Choi |
| author_facet | Ja Hye Kim Yunha Choi Soojin Hwang Ji-Hee Yoon Jieun Lee Min Jae Kang Gu-Hwan Kim Han-Wook Yoo Jin-Ho Choi |
| author_sort | Ja Hye Kim |
| collection | DOAJ |
| description | Objective: This study was performed to investigate the molecular characteristics and frequency of copy number variations (CNVs) of ANOS1 in patients with Kallmann syndrome (KS) or normosmic isolated hypogonadotropic hypogonadism (nIHH) using multiplex ligation-dependent probe amplification (MLPA) analysis and sequencing.
Methods: Among 45 patients from 43 independent families, Sanger sequencing, next-generation sequencing (NGS), or microarray was performed in 24 patients from 23 families, and MLPA was performed in 19 patients who did not sho w rare sequence variants (n = 18) or ANOS1 amplification by PCR (n = 1).
Results: Seven patients (four patients with KS, one patient with nIHH, one prepubertal boy with anosmia, and one newborn patient) from six families (6/43, 14%) harbored molecular defects in ANOS1 including a nonsense mutation (c.1140G>A (p.W380*)), a frameshift mutation (c.1260del (p.Q421Kfs*61)), a splice site m utation (c.1449+1G>A), an exon 7 deletion, a complete deletion, and 7.9 Mb-sized inversio n encompassing ANOS1. The complete deletion of ANOS1 was identified in a neonate with a micropenis and cryptorchidism. Unilateral renal agenesis was found in three pa tients, whereas only one patient displayed both synkinesia and sensorineural hearing los s. There was no reversal of hypogonadotropic hypogonadism in any patient during 9.1 ± 2. 9 years of treatment with testosterone enanthate.
Conclusions: Molecular defects in the ANOS1 gene could be identified in 14% of probands including various types of CNVs (3/43, 7.0%). Comprehensive ana lysis using sequencing and analysis for CNVs is required to detect molecular defects in ANOS1. |
| first_indexed | 2024-04-09T16:52:10Z |
| format | Article |
| id | doaj.art-368140b25ade47a79889160fc12b6735 |
| institution | Directory Open Access Journal |
| issn | 2049-3614 |
| language | English |
| last_indexed | 2024-04-09T16:52:10Z |
| publishDate | 2023-04-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-368140b25ade47a79889160fc12b67352023-04-21T09:50:37ZengBioscientificaEndocrine Connections2049-36142023-04-01125111https://doi.org/10.1530/EC-22-0413Mutation spectrum and frequency of copy number variations of the ANOS1 gene in patients with Kallmann syndrome or normosmic isolated hypogonadotropic hypogonadismJa Hye Kim0Yunha Choi1Soojin Hwang2Ji-Hee Yoon3Jieun Lee4Min Jae Kang5Gu-Hwan Kim6Han-Wook Yoo7Jin-Ho Choi8Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KoreaDepartment of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KoreaDepartment of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KoreaDepartment of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KoreaDepartment of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, KoreaDepartment of Pediatrics, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, KoreaMedical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KoreaDepartment of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KoreaDepartment of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KoreaObjective: This study was performed to investigate the molecular characteristics and frequency of copy number variations (CNVs) of ANOS1 in patients with Kallmann syndrome (KS) or normosmic isolated hypogonadotropic hypogonadism (nIHH) using multiplex ligation-dependent probe amplification (MLPA) analysis and sequencing. Methods: Among 45 patients from 43 independent families, Sanger sequencing, next-generation sequencing (NGS), or microarray was performed in 24 patients from 23 families, and MLPA was performed in 19 patients who did not sho w rare sequence variants (n = 18) or ANOS1 amplification by PCR (n = 1). Results: Seven patients (four patients with KS, one patient with nIHH, one prepubertal boy with anosmia, and one newborn patient) from six families (6/43, 14%) harbored molecular defects in ANOS1 including a nonsense mutation (c.1140G>A (p.W380*)), a frameshift mutation (c.1260del (p.Q421Kfs*61)), a splice site m utation (c.1449+1G>A), an exon 7 deletion, a complete deletion, and 7.9 Mb-sized inversio n encompassing ANOS1. The complete deletion of ANOS1 was identified in a neonate with a micropenis and cryptorchidism. Unilateral renal agenesis was found in three pa tients, whereas only one patient displayed both synkinesia and sensorineural hearing los s. There was no reversal of hypogonadotropic hypogonadism in any patient during 9.1 ± 2. 9 years of treatment with testosterone enanthate. Conclusions: Molecular defects in the ANOS1 gene could be identified in 14% of probands including various types of CNVs (3/43, 7.0%). Comprehensive ana lysis using sequencing and analysis for CNVs is required to detect molecular defects in ANOS1.https://ec.bioscientifica.com/view/journals/ec/12/5/EC-22-0413.xmlanos1copy number variationkallmann syndromemultiplex ligation-dependent probe amplificationhypogonadotropic hypogonadism |
| spellingShingle | Ja Hye Kim Yunha Choi Soojin Hwang Ji-Hee Yoon Jieun Lee Min Jae Kang Gu-Hwan Kim Han-Wook Yoo Jin-Ho Choi Mutation spectrum and frequency of copy number variations of the ANOS1 gene in patients with Kallmann syndrome or normosmic isolated hypogonadotropic hypogonadism Endocrine Connections anos1 copy number variation kallmann syndrome multiplex ligation-dependent probe amplification hypogonadotropic hypogonadism |
| title | Mutation spectrum and frequency of copy number variations of the ANOS1 gene in patients with Kallmann syndrome or normosmic isolated hypogonadotropic hypogonadism |
| title_full | Mutation spectrum and frequency of copy number variations of the ANOS1 gene in patients with Kallmann syndrome or normosmic isolated hypogonadotropic hypogonadism |
| title_fullStr | Mutation spectrum and frequency of copy number variations of the ANOS1 gene in patients with Kallmann syndrome or normosmic isolated hypogonadotropic hypogonadism |
| title_full_unstemmed | Mutation spectrum and frequency of copy number variations of the ANOS1 gene in patients with Kallmann syndrome or normosmic isolated hypogonadotropic hypogonadism |
| title_short | Mutation spectrum and frequency of copy number variations of the ANOS1 gene in patients with Kallmann syndrome or normosmic isolated hypogonadotropic hypogonadism |
| title_sort | mutation spectrum and frequency of copy number variations of the anos1 gene in patients with kallmann syndrome or normosmic isolated hypogonadotropic hypogonadism |
| topic | anos1 copy number variation kallmann syndrome multiplex ligation-dependent probe amplification hypogonadotropic hypogonadism |
| url | https://ec.bioscientifica.com/view/journals/ec/12/5/EC-22-0413.xml |
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