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Interdisciplinary CompetenceMolecular Diagnostics
Know how in the analysis of genetic material.
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Illness46XY infertility / sterility, differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for 46XY infertility / sterility comprising 10 guideline-curated and altogether some 109 curated genes according to the clinical signs

ID
IP9876
Number of genes
74 Accredited laboratory test
Examined sequence length
55,1 kb (Core-/Core-canditate-Genes)
176,3 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

[Sanger]

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GReferenz-Seq.Heredity
ADGRG23081NM_001079858.3XL
AMH1683NM_000479.5AR
AMHR21722NM_020547.3AR
ANOS12043NM_000216.4XLR
AR2763NM_000044.6XLR
AURKC930NM_001015878.2AR
CFTR4443NM_000492.4AD, AR
CHD78994NM_017780.4AD
CYP11A11566NM_000781.3AR, AD
CYP11B11512NM_000497.4AR
CYP17A11527NM_000102.4AR
CYP19A11512NM_031226.3AR
CYP21A21488NM_000500.9AR
FGFR12469NM_023110.3AR
GNRHR987NM_000406.3AR
HSD17B3933NM_000197.2AR
HSD3B21119NM_000198.4AR
KISS1R1197NM_032551.5AR
LHB426NM_000894.3AR
LHCGR2100NM_000233.4AD, AR
NR0B11413NM_000475.5XL
NR5A11386NM_004959.5AD, AR
POU1F1876NM_000306.4AD, AR
PROKR21155NM_144773.4AD, AR
PROP1681NM_006261.5AR
SOX101401NM_006941.4AD
SRD5A2764NM_000348.4AR
SRY615NM_003140.3YL
TACR31398NM_001059.3AR
TEX112822NM_031276.3XLR
APOA1804NM_000039.3AD
BNC23297NM_017637.6AD
CATSPER21593NM_172095.4n.k.
CCDC1414895NM_173648.4AD, AR
CCDC392826NM_181426.2AR
CCDC403429NM_017950.4AR
CDC14A2176NM_033312.3AR
CEP2907440NM_025114.4AR
CFAP2513505NM_144668.6AR
CFAP435231NM_025145.7AR
CFAP445815NM_001164496.2AR
CFAP692914NM_001039706.3AR
DMRT11122NM_021951.3AD
DNAAF22370NM_018139.3AR
DNAAF41131NM_001033559.3AD, AR
DNAAF6651NM_001169154.2XLR
DNAH112798NM_015512.5AR
DPY19L22277NM_173812.5AR
FANCA4368NM_000135.4AR
FANCM6147NM_020937.4AR, Sus
FGF8735NM_033163.5AD
FSHB390NM_000510.4AR
FSHR2088NM_000145.4AR
GATA41329NM_002052.5AD
GNRH1291NM_000825.3AR
HS6ST11236NM_004807.3AD
INSL3474NM_005543.4AD
KLHL101827NM_152467.5AD
MAMLD12325NM_005491.4XLR
PLCZ11827NM_033123.4AR
PLXNA15691NM_032242.4n.k.
PMFBP13170NM_031293.3AR
PROK2390NM_001126128.2AD, AR
RSPO1792NM_001038633.4AR
SEMA3A2316NM_006080.3AD
SOX2954NM_003106.4AD
SOX31341NM_005634.3XL
SOX91530NM_000346.4AD
SUN51397NM_080675.4AR
SYCP3711NM_153694.5AD
TEX159537NM_001350162.2AR
WDR113675NM_018117.12AD
WT11569NM_024426.6AD, SMu
XRCC2843NM_005431.2AR

Informations about the disease

Clinical Comment

Infertility is defined as the inability to become pregnant within one year of unprotected sexual intercourse. Approximately 7% of the male population is affected, which explains the infertility in half of all affected couples. The etiology of male infertility is very complex, and at least 15% of all infertile men show genetic abnormalities. The critical causes of male infertility include sexual differentiation, genitourinary system development, and gametogenesis. Sex chromosome abnormalities play an important role in severe impairments of spermatogenesis, and at least 2,000 genes are involved in spermatogenesis. Nearly a quarter of the known genetic factors contributing to male infertility result in azoospermia. Autosomal gene mutations mainly cause central hypogonadism, teratozoospermia or asthenozoospermia, congenital obstructive azoospermia, and familial cases of quantitative spermatogenesis disorders. Genetic diagnoses begin with karyotyping, deletion analysis of azoospermia factor (AZF) and mutation analysis in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Currently, molecular genetic diagnosis can be confirmed in approximately 5% of infertile men using a more comprehensive gene panel. An inconspicuous genetic finding does not imply exclusion of the suspected clinical diagnosis.

References: https://pubmed.ncbi.nlm.nih.gov/29622783/

https://doi.org/10.1093/humrep/dez022

https://pubmed.ncbi.nlm.nih.gov/31347970/

 

Synonyms
  • Alias: Asthenospermia
  • Alias: Asthenospermie
  • Alias: Azoospermia
  • Alias: Azoospermie
  • Alias: Oligospermia
  • Alias: Oligospermie
  • Allelic: Acampomelic campomelic dysplasia (SOX9)
  • Allelic: Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency (CYP21A2)
  • Allelic: Aldosteronism, glucocorticoid-remediable (CYP11B1)
  • Allelic: Atrial septal defect 2 (GATA4)
  • Allelic: Atrioventricular septal defect 4 (GATA4)
  • Allelic: Campomelic dysplasia (SOX9)
  • Allelic: Cystic fibrosis (CFTR)
  • Allelic: Deafness, AD 34, with/-out inflammation (NLRP3)
  • Allelic: Dyslexia, susceptibility to, 1 (DNAAF4)
  • Allelic: Encephalitis/encephalopathy, mild, with reversible myelin vacuolization (MYRF)
  • Allelic: Familial cold inflammatory syndrome 1 (NLRP3)
  • Allelic: Hydrocephalus, normal pressure, 1 (CFAP43)
  • Allelic: Hypertrypsinemia, neonatal (CFTR)
  • Allelic: Keratoendothelitis fugax hereditaria (NLRP3)
  • Allelic: Leber congenital amaurosis 10 (CEP290)
  • Allelic: Mesothelioma, somatic (WT1)
  • Allelic: Nephrotic syndrome, type 4 (WT1)
  • Allelic: Ovarian dysgenesis 1 (FSHR)
  • Allelic: Ovarian hyperstimulation syndrome (FSHR)
  • Allelic: Ovarian response to FSH stimulation (FSHR)
  • Allelic: Pancreatitis, hereditary (CFTR)
  • Allelic: Pregnancy loss, recurrent, 4 (SYCP3)
  • Allelic: Premature ovarian failure 15 (FANCM)
  • Allelic: Premature ovarian failure 17 (XRCC2)
  • Allelic: Primary ovary insufficiency [panelapp] (IGSF10)
  • Allelic: Prostate cancer, susceptibility to (AR)
  • Allelic: Spinal + bulbar muscular atrophy of Kennedy (AR repeat)
  • Allelic: Sweat chloride elevation without CF (CFTR)
  • Allelic: Tetralogy of Fallot (GATA4)
  • Allelic: Ventricular septal defect 1 (GATA4)
  • Allelic: Wilms tumor, type 1 (WT1)
  • 17,20-lyase deficiency, isolated (CYP17A1)
  • 17-alpha-hydroxylase/17,20-lyase deficiency (CYP17A1)
  • 46XY sex reversal 11 (DHX37)
  • Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency (CYP11B1)
  • Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete (CYP11A1)
  • Amyloidosis, 3 or more types (APOA1)
  • Androgen insensitivity (AR)
  • Androgen insensitivity, partial, with/-out breast cancer (AR)
  • Anosmic hypogonadotropic hypogonadism [panelapp] (CCDC141)
  • Aromatase deficiency (CYP19A1)
  • Aromatase excess syndrome (CYP19A1)
  • Bardet-Biedl syndrome 14 (CEP290)
  • Bronchiectasis with/-out elevated sweat chloride 1, modifier of (CFTR)
  • CINCA syndrome (NLRP3)
  • Campomelic dysplasia with autosomal sex reversal (SOX9)
  • Cardiac-urogenital syndrome (MYRF)
  • Ciliary dyskinesia, primary, 10 (DNAAF2)
  • Ciliary dyskinesia, primary, 14 (CCDC39)
  • Ciliary dyskinesia, primary, 15 (CCDC40)
  • Ciliary dyskinesia, primary, 25 (DNAAF4)
  • Ciliary dyskinesia, primary, 3, with/-out situs inversus (DNAH5)
  • Ciliary dyskinesia, primary, 32 (RSPH3)
  • Ciliary dyskinesia, primary, 36, XL (DNAAF6)
  • Ciliary dyskinesia, primary, 37 (DNAH1)
  • Ciliary dyskinesia, primary, 7, with/-out situs inversus (DNAH11)
  • Congenital bilateral absence of vas deferens (CFTR)
  • Congenital hypogonadotropic hypogonadism [MONDO:0015770] (CCDC141)
  • Cryptorchidism (INSL3)
  • Deafness, AR 32, with/-out immotile sperm /CDC14A)
  • Deafness, autosomal recessive 32, with or without immotile sperm (CDC14A)
  • Delayed puberty [panelapp] (IGSF10)
  • Denys-Drash syndrome (WT1)
  • Fanconi anemia compelmentation group A (FANCA)
  • Fanconi anemia, complementation group U (XRCC2)
  • Frasier syndrome (WT1)
  • Heterotaxy, visceral, 9, autosomal, with male infertility (MNS1)
  • Hydatidiform mole, recurrent, 3 (MEI1)
  • Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency (CYP21A2)
  • Hypoalphalipoproteinemia, primary, 2 (APOA1)
  • Hypoalphalipoproteinemia, primary, 2, intermediate (APOA1)
  • Hypogonadotropic hypogonadism 1 with/-out anosmia; Kallmann syndrome 1 (ANOS1)
  • Hypogonadotropic hypogonadism 11 with/-out anosmia (TACR3)
  • Hypogonadotropic hypogonadism 12 with/-out anosmia (GNRH1)
  • Hypogonadotropic hypogonadism 14 with/-out anosmia (WDR11)
  • Hypogonadotropic hypogonadism 15 with/-out anosmia (HS6ST1)
  • Hypogonadotropic hypogonadism 16 with/-out anosmia (SEMA3A)
  • Hypogonadotropic hypogonadism 18 with/-out anosmia (IL17RD)
  • Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
  • Hypogonadotropic hypogonadism 20 with/-out anosmia (FGF17)
  • Hypogonadotropic hypogonadism 23 with/-out anosmia (LHB)
  • Hypogonadotropic hypogonadism 24 without anosmia (FSHB)
  • Hypogonadotropic hypogonadism 3 with/-out anosmia (PROKR2)
  • Hypogonadotropic hypogonadism 4 with/-out anosmia (PROK2)
  • Hypogonadotropic hypogonadism 6 with/-out anosmia (FGF8)
  • Hypogonadotropic hypogonadism 7 without anosmia (GNRHR)
  • Hypogonadotropic hypogonadism [panelapp] (IGSF10)
  • Hypospadias 2, XL (MAMLD1)
  • Infertility, male [jte-titled from lit.] (DDX3Y)
  • Intellectual developmental disorder, XL, with isolated growth hormone deficiency (SOX3)
  • Joubert syndrome 5 (CEP290)
  • Lipoid adrenal hyperplasia (STAR)
  • Lower urinary tract obstruction, congenital (BNC2)
  • Meacham syndrome (WT1)
  • Meckel syndrome 4 (CEP290)
  • Microphthalmia, syndromic 3 (SOX2)
  • Microphthalmia, syndromic 6 (BPM4)
  • Muckle-Wells syndrome (NLRP3)
  • Neurodevelopmental disorder with brain anomalies with/-out vertebral/cardiac anomalies (DHX37)
  • Optic nerve hypoplasia + abnormalities of the central nervous system (SOX2)
  • Orofacial cleft 11 (BPM4)
  • Palmoplantar hyperkeratosis + true hermaphroditism (RSPO1)
  • Palmoplantar hyperkeratosis with squamous cell carcinoma of skin + sex reversal (RSPO1)
  • Panhypopituitarism, XL (SOX3)
  • Pituitary hormone deficiency, combined or isolated, 1 (POU1F1)
  • Pituitary hormone deficiency, combined, 2 (PROP1)
  • Polycystic kidney disease 1 (PKD1)
  • Pseudovaginal perineoscrotal hypospadias (SRD5A2)
  • Senior-Loken syndrome 6 (CEP290)
  • Spermatogenic failure (HSF2)
  • Spermatogenic failure 1 (SYCP2)
  • Spermatogenic failure 10 (SEPTIN12)
  • Spermatogenic failure 11 (KLHL10)
  • Spermatogenic failure 16 (SUN5)
  • Spermatogenic failure 17 (PLCZ1)
  • Spermatogenic failure 18 (DNAH1)
  • Spermatogenic failure 19 (CFAP43)
  • Spermatogenic failure 20 (CFAP44)
  • Spermatogenic failure 23 (TEX14)
  • Spermatogenic failure 24 (CFAP69)
  • Spermatogenic failure 25 (TEX15)
  • Spermatogenic failure 26 (TSGA10)
  • Spermatogenic failure 28 (FANCM)
  • Spermatogenic failure 31 (PMFBP1)
  • Spermatogenic failure 33 (CFAP251)
  • Spermatogenic failure 34 (FSIP2)
  • Spermatogenic failure 35 (QRICH2)
  • Spermatogenic failure 38 (ARMC2)
  • Spermatogenic failure 39 (DNAH17)
  • Spermatogenic failure 4 (SYCP3)
  • Spermatogenic failure 40 (CFAP65)
  • Spermatogenic failure 42 (TTC29)
  • Spermatogenic failure 43 (SPEF2)
  • Spermatogenic failure 48 (M1AP)
  • Spermatogenic failure 50 (XRCC2)
  • Spermatogenic failure 51 (CFAP91)
  • Spermatogenic failure 6 (SPATA16)
  • Spermatogenic failure, XL 2 (TEX11)
  • Testicular anomalies with/-out congenital heart disease (GATA4)
Heredity, heredity patterns etc.
  • AD
  • AR
  • SMu
  • Sus
  • XL
  • XLR
  • YL
  • n.k.
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

No text defined