Spermatogenic failure, x-linked, 8(SPGFX8)

MedGen UID:: 1858665
•Concept ID:: C5935568
•: Disease or Syndrome

Synonyms:	SPERMATOGENIC FAILURE, X-LINKED, 8; SPGFX8

Gene (location): Gene(s) directly associated with this condition or phenotype.	CYLC1 (Xq21.1)

Monarch Initiative:	MONDO:0970943
OMIM®:	301119

Definition

X-linked spermatogenic failure-8 (SPGFX8) is characterized by male infertility associated with markedly reduced progressive sperm motility. Patient sperm show head and midpiece defects, with deformed and detached acrosomes (Schneider et al., 2023; Jin et al., 2024). For a general phenotypic description and discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). [from OMIM]

Clinical features

From HPO

Male infertility

MedGen UID:: 5796
•Concept ID:: C0021364
•: Disease or Syndrome

The inability of the male to effect fertilization of an ovum after a specified period of unprotected intercourse. Male sterility is permanent infertility.

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Oligozoospermia

MedGen UID:: 678638
•Concept ID:: C0868910
•: Finding

Reduced count of spermatozoa in the semen, defined as a sperm count below 20 million per milliliter semen.

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Abnormal sperm head morphology

MedGen UID:: 868308
•Concept ID:: C4022702
•: Finding

A structural abnormality of the sperm head.

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Coiled sperm flagella

MedGen UID:: 1611216
•Concept ID:: C4539789
•: Finding

Sperm cells whose flagella are twisted (coiled).

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Reduced progressive sperm motility

MedGen UID:: 1730031
•Concept ID:: C5436680
•: Finding

A reduced proportion of sperm that move in a straight line or large circles; alternatively, an increased proportion of sperm that move in tight circles or in some other non-linear fashion.

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Abnormality of the genitourinary system

Recent clinical studies

Etiology

Variants in GCNA, X-linked germ-cell genome integrity gene, identified in men with primary spermatogenic failure.

Hardy JJ, Wyrwoll MJ, Mcfadden W, Malcher A, Rotte N, Pollock NC, Munyoki S, Veroli MV, Houston BJ, Xavier MJ, Kasak L, Punab M, Laan M, Kliesch S, Schlegel P, Jaffe T, Hwang K, Vukina J, Brieño-Enríquez MA, Orwig K, Yanowitz J, Buszczak M, Veltman JA, Oud M, Nagirnaja L, Olszewska M, O'Bryan MK, Conrad DF, Kurpisz M, Tüttelmann F, Yatsenko AN; GEMINI Consortium
Hum Genet 2021 Aug;140(8):1169-1182. Epub 2021 May 7 doi: 10.1007/s00439-021-02287-y. PMID: 33963445 Free PMC Article

Mutation analysis of the X-chromosome linked, testis-specific TAF7L gene in spermatogenic failure.

Akinloye O, Gromoll J, Callies C, Nieschlag E, Simoni M
Andrologia 2007 Oct;39(5):190-5. doi: 10.1111/j.1439-0272.2007.00789.x. PMID: 17714218

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Diagnosis

Genomic testing for copy number and single nucleotide variants in spermatogenic failure.

Hardy J, Pollock N, Gingrich T, Sweet P, Ramesh A, Kuong J, Basar A, Jiang H, Hwang K, Vukina J, Jaffe T, Olszewska M, Kurpisz M, Yatsenko AN
J Assist Reprod Genet 2022 Sep;39(9):2103-2114. Epub 2022 Jul 18 doi: 10.1007/s10815-022-02538-5. PMID: 35849255 Free PMC Article

Large-scale analyses of the X chromosome in 2,354 infertile men discover recurrently affected genes associated with spermatogenic failure.

Riera-Escamilla A, Vockel M, Nagirnaja L, Xavier MJ, Carbonell A, Moreno-Mendoza D, Pybus M, Farnetani G, Rosta V, Cioppi F, Friedrich C, Oud MS, van der Heijden GW, Soave A, Diemer T, Ars E, Sánchez-Curbelo J, Kliesch S, O'Bryan MK, Ruiz-Castañe E; GEMINI Consortium, Azorín F, Veltman JA, Aston KI, Conrad DF, Tüttelmann F, Krausz C
Am J Hum Genet 2022 Aug 4;109(8):1458-1471. Epub 2022 Jul 8 doi: 10.1016/j.ajhg.2022.06.007. PMID: 35809576 Free PMC Article

Variants in GCNA, X-linked germ-cell genome integrity gene, identified in men with primary spermatogenic failure.

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