A Gly684Ala substitution in the androgen receptor is the cause for azoospermia in a Chinese family with mild androgen insensitivity syndrome and normal hormone levels
Androgen receptor gene (AR) is essential for male growth and fertility. Its mutations are responsible for androgen insensitivity syndrome (AIS) that usually shows the phenotype of azoospermia resulting in male infertility. This study reported the first case of mild AIS with complete normal serum hor...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.988202/full |
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| author | Yuan Yuan Wen-Qing Xu Ying Chen Ying Chen Tao Luo Tao Luo Hou-Yang Chen Hou-Yang Chen |
| author_facet | Yuan Yuan Wen-Qing Xu Ying Chen Ying Chen Tao Luo Tao Luo Hou-Yang Chen Hou-Yang Chen |
| author_sort | Yuan Yuan |
| collection | DOAJ |
| description | Androgen receptor gene (AR) is essential for male growth and fertility. Its mutations are responsible for androgen insensitivity syndrome (AIS) that usually shows the phenotype of azoospermia resulting in male infertility. This study reported the first case of mild AIS with complete normal serum hormones in a Chinese family. The proband referred for infertility because of azoospermia. His uncle and two cousins are both infertile and have azoospermia. Whole-exome sequencing in the genetic analyses showed that the proband carries a novel hemizygous AR missense mutation, NM_000044.6: c.2051G>C (p.Gly684Ala), in exon four within the ligand-binding domain. His mother and maternal aunt are heterozygous carriers, while his father and brother are wildtype, indicating that the mutation in the proband was inherited from his mother. This pattern is consistent with the genetic model of the X-linked recessive inheritance of AR in AIS pathogenesis. HOPE predicts that p.Gly684Ala increases the hydrophobicity of AR but does not change the AR conformation. PolyPhen-2 predicts that p.Gly684Ala is harmful. This study provides the new knowledge to understand the AR gene mutations in MAIS. |
| first_indexed | 2024-04-11T12:06:33Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T12:06:33Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-ca1db8361fb74141a0b6b89a860e11512022-12-22T04:24:42ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.988202988202A Gly684Ala substitution in the androgen receptor is the cause for azoospermia in a Chinese family with mild androgen insensitivity syndrome and normal hormone levelsYuan Yuan0Wen-Qing Xu1Ying Chen2Ying Chen3Tao Luo4Tao Luo5Hou-Yang Chen6Hou-Yang Chen7Institute of Life Science and School of Life Science, Nanchang University, Nanchang, Jiangxi, ChinaInstitute of Life Science and School of Life Science, Nanchang University, Nanchang, Jiangxi, ChinaInstitute of Life Science and School of Life Science, Nanchang University, Nanchang, Jiangxi, ChinaKey Laboratory of Reproductive Physiology and Pathology in Jiangxi Province, Nanchang, Jiangxi, ChinaInstitute of Life Science and School of Life Science, Nanchang University, Nanchang, Jiangxi, ChinaKey Laboratory of Reproductive Physiology and Pathology in Jiangxi Province, Nanchang, Jiangxi, ChinaReproductive Medical Center, Jiangxi Maternal and Child Health Hospital, Affiliated Maternal and Child Health Hospital of Nanchang University, Nanchang, Jiangxi, ChinaKey Laboratory of Reproductive Physiology and Pathology in Jiangxi Province, Nanchang, Jiangxi, ChinaAndrogen receptor gene (AR) is essential for male growth and fertility. Its mutations are responsible for androgen insensitivity syndrome (AIS) that usually shows the phenotype of azoospermia resulting in male infertility. This study reported the first case of mild AIS with complete normal serum hormones in a Chinese family. The proband referred for infertility because of azoospermia. His uncle and two cousins are both infertile and have azoospermia. Whole-exome sequencing in the genetic analyses showed that the proband carries a novel hemizygous AR missense mutation, NM_000044.6: c.2051G>C (p.Gly684Ala), in exon four within the ligand-binding domain. His mother and maternal aunt are heterozygous carriers, while his father and brother are wildtype, indicating that the mutation in the proband was inherited from his mother. This pattern is consistent with the genetic model of the X-linked recessive inheritance of AR in AIS pathogenesis. HOPE predicts that p.Gly684Ala increases the hydrophobicity of AR but does not change the AR conformation. PolyPhen-2 predicts that p.Gly684Ala is harmful. This study provides the new knowledge to understand the AR gene mutations in MAIS.https://www.frontiersin.org/articles/10.3389/fgene.2022.988202/fullandrogen insensitivity syndromeandrogen receptorazoospermiahormoneinfertility |
| spellingShingle | Yuan Yuan Wen-Qing Xu Ying Chen Ying Chen Tao Luo Tao Luo Hou-Yang Chen Hou-Yang Chen A Gly684Ala substitution in the androgen receptor is the cause for azoospermia in a Chinese family with mild androgen insensitivity syndrome and normal hormone levels Frontiers in Genetics androgen insensitivity syndrome androgen receptor azoospermia hormone infertility |
| title | A Gly684Ala substitution in the androgen receptor is the cause for azoospermia in a Chinese family with mild androgen insensitivity syndrome and normal hormone levels |
| title_full | A Gly684Ala substitution in the androgen receptor is the cause for azoospermia in a Chinese family with mild androgen insensitivity syndrome and normal hormone levels |
| title_fullStr | A Gly684Ala substitution in the androgen receptor is the cause for azoospermia in a Chinese family with mild androgen insensitivity syndrome and normal hormone levels |
| title_full_unstemmed | A Gly684Ala substitution in the androgen receptor is the cause for azoospermia in a Chinese family with mild androgen insensitivity syndrome and normal hormone levels |
| title_short | A Gly684Ala substitution in the androgen receptor is the cause for azoospermia in a Chinese family with mild androgen insensitivity syndrome and normal hormone levels |
| title_sort | gly684ala substitution in the androgen receptor is the cause for azoospermia in a chinese family with mild androgen insensitivity syndrome and normal hormone levels |
| topic | androgen insensitivity syndrome androgen receptor azoospermia hormone infertility |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.988202/full |
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