Details of Disease

General Information of Disease (ID: DISG7641)

• Disease Name: Obsolete non-syndromic male infertility due to sperm motility disorder
• Synonyms: non-syndromic male infertility due asthenozoospermia; isolated male infertility due to sperm motility disorder; nonsyndromic male infertility due to sperm motility disorder
• Definition: OBSOLETE. Non-syndromic male infertility due to sperm motility disorder is a rare, genetic, non-syndromic male infertility disorder characterized by infertility due to sperm with defects in their cilia/flagella structure, leading to absent motility or reduced forward motility in fresh ejaculate. Reduced semen volume, oligospermia and an increased number of abnormally structured spermatozoa is often present.
• Disease Hierarchy:
  DIS01GPL: Grass pollen hypersensitivity
  DISG7641: Obsolete non-syndromic male infertility due to sperm motility disorder

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CATSPER1	TT5CISB	Supportive	Autosomal recessive	[1]

This Disease Is Related to 19 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ACTL9	OTDOBD9M	Supportive	Autosomal recessive	[2]
AK7	OTASZDJN	Supportive	Autosomal recessive	[3]
ARMC2	OTMCC01T	Supportive	Autosomal recessive	[4]
CATSPER1	OTPCTSQZ	Supportive	Autosomal recessive	[1]
CFAP251	OT0GKNAU	Supportive	Autosomal recessive	[5]
CFAP43	OT6R8UGG	Supportive	Autosomal recessive	[6]
CFAP44	OT1273MD	Supportive	Autosomal recessive	[6]
CFAP65	OTGB5HVT	Supportive	Autosomal recessive	[7]
CFAP69	OTK73MCA	Supportive	Autosomal recessive	[8]
CFAP70	OTIRTNXU	Supportive	Autosomal recessive	[9]
DNAH1	OTDZ26FJ	Supportive	Autosomal recessive	[10]
DNAH17	OT4G6E70	Supportive	Autosomal recessive	[11]
FSIP2	OTM9VKX1	Supportive	Autosomal recessive	[12]
SEPTIN12	OTFUKRXA	Supportive	Autosomal recessive	[13]
SLC26A8	OTNCW8RJ	Supportive	Autosomal recessive	[14]
SPAG17	OTUF58WZ	Supportive	Autosomal recessive	[15]
SPEF2	OTO04K1T	Supportive	Autosomal recessive	[16]
TTC21A	OTBJ9JKF	Supportive	Autosomal recessive	[17]
TTC29	OT37KCUL	Supportive	Autosomal recessive	[18]

References

• [1] Human male infertility caused by mutations in the CATSPER1 channel protein. Am J Hum Genet. 2009 Apr;84(4):505-10. doi: 10.1016/j.ajhg.2009.03.004. Epub 2009 Apr 2.
• [2] Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice. Am J Hum Genet. 2021 Mar 4;108(3):469-481. doi: 10.1016/j.ajhg.2021.02.004. Epub 2021 Feb 23.
• [3] Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia. Hum Mol Genet. 2018 Apr 1;27(7):1196-1211. doi: 10.1093/hmg/ddy034.
• [4] Bi-allelic Mutations in ARMC2 Lead to Severe Astheno-Teratozoospermia Due to Sperm Flagellum Malformations in Humans and Mice. Am J Hum Genet. 2019 Feb 7;104(2):331-340. doi: 10.1016/j.ajhg.2018.12.013. Epub 2019 Jan 24.
• [5] A Homozygous Ancestral SVA-Insertion-Mediated Deletion in WDR66 Induces Multiple Morphological Abnormalities of the Sperm Flagellum and Male Infertility. Am J Hum Genet. 2018 Sep 6;103(3):400-412. doi: 10.1016/j.ajhg.2018.07.014. Epub 2018 Aug 16.
• [6] Biallelic Mutations in CFAP43 and CFAP44 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella. Am J Hum Genet. 2017 Jun 1;100(6):854-864. doi: 10.1016/j.ajhg.2017.04.012. Epub 2017 May 25.
• [7] Biallelic mutations in CFAP65 lead to severe asthenoteratospermia due to acrosome hypoplasia and flagellum malformations. J Med Genet. 2019 Nov;56(11):750-757. doi: 10.1136/jmedgenet-2019-106031. Epub 2019 Aug 14.
• [8] Absence of CFAP69 Causes Male Infertility due to Multiple Morphological Abnormalities of the Flagella in Human and Mouse. Am J Hum Genet. 2018 Apr 5;102(4):636-648. doi: 10.1016/j.ajhg.2018.03.007.
• [9] CFAP70 mutations lead to male infertility due to severe astheno-teratozoospermia. A case report. Hum Reprod. 2019 Oct 2;34(10):2071-2079. doi: 10.1093/humrep/dez166.
• [10] Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella. Am J Hum Genet. 2014 Jan 2;94(1):95-104. doi: 10.1016/j.ajhg.2013.11.017. Epub 2013 Dec 19.
• [11] Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Outer Dynein Arm Heavy Chain, Cause Isolated Male Infertility Due to Asthenozoospermia. Am J Hum Genet. 2019 Jul 3;105(1):198-212. doi: 10.1016/j.ajhg.2019.04.015. Epub 2019 Jun 6.
• [12] Whole-exome sequencing identifies mutations in FSIP2 as a recurrent cause of multiple morphological abnormalities of the sperm flagella. Hum Reprod. 2018 Oct 1;33(10):1973-1984. doi: 10.1093/humrep/dey264.
• [13] SEPT12 mutations cause male infertility with defective sperm annulus. Hum Mutat. 2012 Apr;33(4):710-9. doi: 10.1002/humu.22028. Epub 2012 Feb 20.
• [14] Missense mutations in SLC26A8, encoding a sperm-specific activator of CFTR, are associated with human asthenozoospermia. Am J Hum Genet. 2013 May 2;92(5):760-6. doi: 10.1016/j.ajhg.2013.03.016. Epub 2013 Apr 11.
• [15] A familial study of twins with severe asthenozoospermia identified a homozygous SPAG17 mutation by whole-exome sequencing. Clin Genet. 2018 Feb;93(2):345-349. doi: 10.1111/cge.13059. Epub 2017 Sep 4.
• [16] Loss-of-function mutations in SPEF2 cause multiple morphological abnormalities of the sperm flagella (MMAF). J Med Genet. 2019 Oct;56(10):678-684. doi: 10.1136/jmedgenet-2018-105952. Epub 2019 May 31.
• [17] Bi-allelic Mutations in TTC21A Induce Asthenoteratospermia in Humans and Mice. Am J Hum Genet. 2019 Apr 4;104(4):738-748. doi: 10.1016/j.ajhg.2019.02.020. Epub 2019 Mar 28.
• [18] Mutations in TTC29, Encoding an Evolutionarily Conserved Axonemal Protein, Result in Asthenozoospermia and Male Infertility. Am J Hum Genet. 2019 Dec 5;105(6):1148-1167. doi: 10.1016/j.ajhg.2019.10.007. Epub 2019 Nov 14.