#619867
Table of Contents
A number sign (#) is used with this entry because of evidence that spermatogenic failure-72 (SPGF72) is caused by homozygous mutation in the WDR19 gene (608151) on chromosome 4p14. One such patient has been reported.
Spermatogenic failure-72 (SPGF72) is characterized by male infertility due to multiple morphologic abnormalities of the flagella (MMAF), including coiled, short, angulated, absent, and irregular-caliber flagella, resulting in lack of sperm motility (Ni et al., 2020).
For a general phenotypic description and discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Ni et al. (2020) reported an infertile Han Chinese man, born of first-cousin parents, with spermatogenic failure and mutation in the WDR19 gene. Semen analysis showed normal volume and sperm concentration, but progressive motility was zero. Sperm morphology showed that more than 85% of patient spermatozoa exhibited typical features of MMAF, including coiled (52%), short (15.5%), angulated (12%), absent (4.5%) and irregular-caliber (2.5%) flagella. Transmission electron microscopy of patient sperm flagella revealed abnormalities in all cross-sections analyzed, predominantly consisting of a vacuolar appearance, with most sperm showing a damaged axoneme and absence of microtubule structures, with only small amounts of debris-like substance present. The remaining sperm contained 9 peripheral microtubule doublets, but lacked the central pair (9+0 configuration). CT imaging showed no anomalies of the long bones, ribs, pelvis, or phalanges, and no hepatic or renal anomalies. Retinal photographs showed normal fundus, macula, and arterioles, and there were no dental anomalies on panoramic x-ray. In addition, laboratory analysis showed normal liver and kidney function. Intracytoplasmic sperm injection (ICSI) resulted in successful pregnancy.
The transmission pattern of SPGF72 in the family reported by Ni et al. (2020) was consistent with autosomal recessive inheritance.
In an infertile Han Chinese man with MMAF, Ni et al. (2020) identified homozygosity for a missense mutation in the WDR19 gene (K1271E; 608151.0020) that segregated with disease in the family and was not found in public variant databases.
By analysis of ejaculates from 794 Brown Swiss bulls and genomewide association testing, Hiltpold et al. (2020) identified a quantitative trait locus (QTL) on bovine chromosome 6 that was associated with sperm motility, head and tail anomalies, and insemination success. The QTL effect was replicated in an independent cohort of 2,481 Brown Swiss bulls. Analysis of whole-genome sequencing data revealed a synonymous variant in the WDR19 gene that was in linkage disequilibrium with the fertility-associated haplotype. Transcription analysis demonstrated that the variant activates a cryptic splice site and eliminates 3 evolutionarily conserved amino acids; Western blot showed reduced WDR19 protein in testicular tissue of heterozygous bulls that was reduced even further in homozygotes. Semen quality of the homozygous bulls was only slightly reduced compared to heterozygous or noncarrier bulls; however, more ejaculates were rejected for artificial insemination due to less than 70% motile sperm in homozygous than either heterozygous or noncarrier bulls, and fertility of homozygous bulls was reduced.
Hiltpold, M., Niu, G., Kadri, N. K., Crysnanto, D., Fang, Z.-H., Spengeler, M., Schmitz-Hsu, F., Fuerst, C., Schwarzenbacher, H., Seefried, F. R., Seehusen, F., Witschi, U., Schnieke, A., Fries, R., Bollwein, H., Flisikowski, K., Pausch, H. Activation of cryptic splicing in bovine WDR19 is associated with reduced semen quality and male fertility. PLoS Genet. 16: e1008804, 2020. [PubMed: 32407316, images, related citations] [Full Text]
Ni, X., Wang, J., Lv, M., Liu, C., Zhong, Y., Tian, S., Wu, H., Cheng, H., Gao, Y., Tan, Q., Chen, B., Li, Q., Song, B., Wei, Z., Zhou, P., He, X., Zhang, F., Cao, Y. A novel homozygous mutation in WDR19 induces disorganization of microtubules in sperm flagella and nonsyndromic asthenoteratospermia. J. Assist. Reprod. Genet. 37: 1431-1439, 2020. [PubMed: 32323121, images, related citations] [Full Text]
ORPHA: 399805; DO: 0070571;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 4p14 | ?Spermatogenic failure 72 | 619867 | Autosomal recessive | 3 | WDR19 | 608151 |
A number sign (#) is used with this entry because of evidence that spermatogenic failure-72 (SPGF72) is caused by homozygous mutation in the WDR19 gene (608151) on chromosome 4p14. One such patient has been reported.
Spermatogenic failure-72 (SPGF72) is characterized by male infertility due to multiple morphologic abnormalities of the flagella (MMAF), including coiled, short, angulated, absent, and irregular-caliber flagella, resulting in lack of sperm motility (Ni et al., 2020).
For a general phenotypic description and discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Ni et al. (2020) reported an infertile Han Chinese man, born of first-cousin parents, with spermatogenic failure and mutation in the WDR19 gene. Semen analysis showed normal volume and sperm concentration, but progressive motility was zero. Sperm morphology showed that more than 85% of patient spermatozoa exhibited typical features of MMAF, including coiled (52%), short (15.5%), angulated (12%), absent (4.5%) and irregular-caliber (2.5%) flagella. Transmission electron microscopy of patient sperm flagella revealed abnormalities in all cross-sections analyzed, predominantly consisting of a vacuolar appearance, with most sperm showing a damaged axoneme and absence of microtubule structures, with only small amounts of debris-like substance present. The remaining sperm contained 9 peripheral microtubule doublets, but lacked the central pair (9+0 configuration). CT imaging showed no anomalies of the long bones, ribs, pelvis, or phalanges, and no hepatic or renal anomalies. Retinal photographs showed normal fundus, macula, and arterioles, and there were no dental anomalies on panoramic x-ray. In addition, laboratory analysis showed normal liver and kidney function. Intracytoplasmic sperm injection (ICSI) resulted in successful pregnancy.
The transmission pattern of SPGF72 in the family reported by Ni et al. (2020) was consistent with autosomal recessive inheritance.
In an infertile Han Chinese man with MMAF, Ni et al. (2020) identified homozygosity for a missense mutation in the WDR19 gene (K1271E; 608151.0020) that segregated with disease in the family and was not found in public variant databases.
By analysis of ejaculates from 794 Brown Swiss bulls and genomewide association testing, Hiltpold et al. (2020) identified a quantitative trait locus (QTL) on bovine chromosome 6 that was associated with sperm motility, head and tail anomalies, and insemination success. The QTL effect was replicated in an independent cohort of 2,481 Brown Swiss bulls. Analysis of whole-genome sequencing data revealed a synonymous variant in the WDR19 gene that was in linkage disequilibrium with the fertility-associated haplotype. Transcription analysis demonstrated that the variant activates a cryptic splice site and eliminates 3 evolutionarily conserved amino acids; Western blot showed reduced WDR19 protein in testicular tissue of heterozygous bulls that was reduced even further in homozygotes. Semen quality of the homozygous bulls was only slightly reduced compared to heterozygous or noncarrier bulls; however, more ejaculates were rejected for artificial insemination due to less than 70% motile sperm in homozygous than either heterozygous or noncarrier bulls, and fertility of homozygous bulls was reduced.
Hiltpold, M., Niu, G., Kadri, N. K., Crysnanto, D., Fang, Z.-H., Spengeler, M., Schmitz-Hsu, F., Fuerst, C., Schwarzenbacher, H., Seefried, F. R., Seehusen, F., Witschi, U., Schnieke, A., Fries, R., Bollwein, H., Flisikowski, K., Pausch, H. Activation of cryptic splicing in bovine WDR19 is associated with reduced semen quality and male fertility. PLoS Genet. 16: e1008804, 2020. [PubMed: 32407316] [Full Text: https://doi.org/10.1371/journal.pgen.1008804]
Ni, X., Wang, J., Lv, M., Liu, C., Zhong, Y., Tian, S., Wu, H., Cheng, H., Gao, Y., Tan, Q., Chen, B., Li, Q., Song, B., Wei, Z., Zhou, P., He, X., Zhang, F., Cao, Y. A novel homozygous mutation in WDR19 induces disorganization of microtubules in sperm flagella and nonsyndromic asthenoteratospermia. J. Assist. Reprod. Genet. 37: 1431-1439, 2020. [PubMed: 32323121] [Full Text: https://doi.org/10.1007/s10815-020-01770-1]
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