DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing

Publication Date:
2018-02-23
Publisher:
BMJ Publishing Group
Print ISSN:
0022-2593
Electronic ISSN:
1468-6244
Topics:
Medicine
Published by:
http://www.bmj.com/
_version_ 1836398807888166912
autor He, W.-B., Tu, C.-F., Liu, Q., Meng, L.-L., Yuan, S.-M., Luo, A.-X., He, F.-S., Shen, J., Li, W., Du, J., Zhong, C.-G., Lu, G.-X., Lin, G., Fan, L.-Q., Tan, Y.-Q.
beschreibung Background The genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown. Objective To identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family. Methods We performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family. In silico analysis was performed to functionally characterise the mutation, and histological analysis was performed using the biopsied testicle sample from the male patient with NOA. Results We identified a novel homozygous missense mutation (NM_007068.3: c.106G〉A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in this family. The identified missense mutation resulted in the substitution of a conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1. This substitution results in protein misfolding. Histological analysis demonstrated a lack of spermatozoa in the male patient’s seminiferous tubules. Immunohistochemistry using a testis biopsy sample from the male patient showed that spermatogenesis was blocked at the zygotene stage during meiotic prophase I. Conclusions To the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree analysis shows an autosomal recessive mode of inheritance for NOA and POI caused by DMC1 in this family.
citation_standardnr 6172916
datenlieferant ipn_articles
feed_id 5627
feed_publisher BMJ Publishing Group
feed_publisher_url http://www.bmj.com/
insertion_date 2018-02-23
journaleissn 1468-6244
journalissn 0022-2593
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher BMJ Publishing Group
quelle Journal of Medical Genetics
relation http://jmg.bmj.com/cgi/content/short/55/3/198?rss=1
search_space articles
shingle_author_1 He, W.-B., Tu, C.-F., Liu, Q., Meng, L.-L., Yuan, S.-M., Luo, A.-X., He, F.-S., Shen, J., Li, W., Du, J., Zhong, C.-G., Lu, G.-X., Lin, G., Fan, L.-Q., Tan, Y.-Q.
shingle_author_2 He, W.-B., Tu, C.-F., Liu, Q., Meng, L.-L., Yuan, S.-M., Luo, A.-X., He, F.-S., Shen, J., Li, W., Du, J., Zhong, C.-G., Lu, G.-X., Lin, G., Fan, L.-Q., Tan, Y.-Q.
shingle_author_3 He, W.-B., Tu, C.-F., Liu, Q., Meng, L.-L., Yuan, S.-M., Luo, A.-X., He, F.-S., Shen, J., Li, W., Du, J., Zhong, C.-G., Lu, G.-X., Lin, G., Fan, L.-Q., Tan, Y.-Q.
shingle_author_4 He, W.-B., Tu, C.-F., Liu, Q., Meng, L.-L., Yuan, S.-M., Luo, A.-X., He, F.-S., Shen, J., Li, W., Du, J., Zhong, C.-G., Lu, G.-X., Lin, G., Fan, L.-Q., Tan, Y.-Q.
shingle_catch_all_1 DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing
Background The genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown. Objective To identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family. Methods We performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family. In silico analysis was performed to functionally characterise the mutation, and histological analysis was performed using the biopsied testicle sample from the male patient with NOA. Results We identified a novel homozygous missense mutation (NM_007068.3: c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in this family. The identified missense mutation resulted in the substitution of a conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1. This substitution results in protein misfolding. Histological analysis demonstrated a lack of spermatozoa in the male patient’s seminiferous tubules. Immunohistochemistry using a testis biopsy sample from the male patient showed that spermatogenesis was blocked at the zygotene stage during meiotic prophase I. Conclusions To the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree analysis shows an autosomal recessive mode of inheritance for NOA and POI caused by DMC1 in this family.
He, W.-B., Tu, C.-F., Liu, Q., Meng, L.-L., Yuan, S.-M., Luo, A.-X., He, F.-S., Shen, J., Li, W., Du, J., Zhong, C.-G., Lu, G.-X., Lin, G., Fan, L.-Q., Tan, Y.-Q.
BMJ Publishing Group
0022-2593
00222593
1468-6244
14686244
shingle_catch_all_2 DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing
Background The genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown. Objective To identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family. Methods We performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family. In silico analysis was performed to functionally characterise the mutation, and histological analysis was performed using the biopsied testicle sample from the male patient with NOA. Results We identified a novel homozygous missense mutation (NM_007068.3: c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in this family. The identified missense mutation resulted in the substitution of a conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1. This substitution results in protein misfolding. Histological analysis demonstrated a lack of spermatozoa in the male patient’s seminiferous tubules. Immunohistochemistry using a testis biopsy sample from the male patient showed that spermatogenesis was blocked at the zygotene stage during meiotic prophase I. Conclusions To the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree analysis shows an autosomal recessive mode of inheritance for NOA and POI caused by DMC1 in this family.
He, W.-B., Tu, C.-F., Liu, Q., Meng, L.-L., Yuan, S.-M., Luo, A.-X., He, F.-S., Shen, J., Li, W., Du, J., Zhong, C.-G., Lu, G.-X., Lin, G., Fan, L.-Q., Tan, Y.-Q.
BMJ Publishing Group
0022-2593
00222593
1468-6244
14686244
shingle_catch_all_3 DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing
Background The genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown. Objective To identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family. Methods We performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family. In silico analysis was performed to functionally characterise the mutation, and histological analysis was performed using the biopsied testicle sample from the male patient with NOA. Results We identified a novel homozygous missense mutation (NM_007068.3: c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in this family. The identified missense mutation resulted in the substitution of a conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1. This substitution results in protein misfolding. Histological analysis demonstrated a lack of spermatozoa in the male patient’s seminiferous tubules. Immunohistochemistry using a testis biopsy sample from the male patient showed that spermatogenesis was blocked at the zygotene stage during meiotic prophase I. Conclusions To the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree analysis shows an autosomal recessive mode of inheritance for NOA and POI caused by DMC1 in this family.
He, W.-B., Tu, C.-F., Liu, Q., Meng, L.-L., Yuan, S.-M., Luo, A.-X., He, F.-S., Shen, J., Li, W., Du, J., Zhong, C.-G., Lu, G.-X., Lin, G., Fan, L.-Q., Tan, Y.-Q.
BMJ Publishing Group
0022-2593
00222593
1468-6244
14686244
shingle_catch_all_4 DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing
Background The genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown. Objective To identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family. Methods We performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family. In silico analysis was performed to functionally characterise the mutation, and histological analysis was performed using the biopsied testicle sample from the male patient with NOA. Results We identified a novel homozygous missense mutation (NM_007068.3: c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in this family. The identified missense mutation resulted in the substitution of a conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1. This substitution results in protein misfolding. Histological analysis demonstrated a lack of spermatozoa in the male patient’s seminiferous tubules. Immunohistochemistry using a testis biopsy sample from the male patient showed that spermatogenesis was blocked at the zygotene stage during meiotic prophase I. Conclusions To the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree analysis shows an autosomal recessive mode of inheritance for NOA and POI caused by DMC1 in this family.
He, W.-B., Tu, C.-F., Liu, Q., Meng, L.-L., Yuan, S.-M., Luo, A.-X., He, F.-S., Shen, J., Li, W., Du, J., Zhong, C.-G., Lu, G.-X., Lin, G., Fan, L.-Q., Tan, Y.-Q.
BMJ Publishing Group
0022-2593
00222593
1468-6244
14686244
shingle_title_1 DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing
shingle_title_2 DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing
shingle_title_3 DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing
shingle_title_4 DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing
timestamp 2025-06-30T23:32:57.253Z
titel DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing
titel_suche DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing
topic WW-YZ
uid ipn_articles_6172916