We have added Female Infertility NGS panel to our Asper Reprogenetics testing menu. List of genes covered by the panel is available www.asperbio.com/asper-reprogenetics/female-infertility-ngs-panel/
List of diseases covered by Female Infertility NGS panel
Published 11/03/2020List of diseases covered by
Female Infertility NGS panel
| Gene | Condition |
| ANOS1 | Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1) |
| AR | Aplasia of the uterus |
| BMP15 | Premature ovarian failure 4 |
| BMP4 | Microphthalmia, syndromic 6; Orofacial cleft 11 |
| CASR | Hyperparathyroidism, neonatal; Hypocalcemia, autosomal dominant; Hypocalciuric hypercalcemia, type I |
| CFTR | Cystic fibrosis |
| CLPP | Perrault syndrome 3 |
| DUOX2 | Thyroid dyshormonogenesis 6 |
| DUOXA2 | Thyroid dyshormonogenesis 5 |
| DUSP6 | Hypogonadotropic hypogonadism 19 with or without anosmia |
| EIF2B1 | Leukoencephalopathy with vanishing white matter |
| EIF2B2 | Ovarioleukodystrophy |
| EIF2B4 | Ovarioleukodystrophy |
| EIF2B5 | Ovarioleukodystrophy |
| ERCC6 | Premature ovarian failure 11 |
| ESR1 | Estrogen resistance |
| ESR2 | Ovarian dysgenesis 8 |
| F2 | Thrombophilia due to thrombin defect; Pregnancy loss, recurrent, susceptibility to, 2 |
| F5 | Thrombophilia due to activated protein C resistance; Factor V deficiency; Pregnancy loss, recurrent, susceptibility to, 1 |
| FEZF1 | Hypogonadotropic hypogonadism 22, with or without anosmia |
| FGF17 | Hypogonadotropic hypogonadism 20 with or without anosmia |
| FGF8 | Hypogonadotropic hypogonadism 6 with or without anosmia |
| FGFR1 | Hypogonadotropic hypogonadism 2 with or without anosmia |
| FIGLA | Premature ovarian failure 6 |
| FLRT3 | Hypogonadotropic hypogonadism 21 with anosmia |
| FMR1 | Premature ovarian failure 1 |
| FOXE1 | Bamforth-Lazarus syndrome |
| FOXL2 | Premature ovarian failure 3 |
| FSHB | Hypogonadotropic hypogonadism 24 without anosmia |
| FSHR | Ovarian dysgenesis 1; Ovarian hyperstimulation syndrome; Ovarian response to FSH stimulation |
| GCM2 | Hyperparathyroidism 4; Hypoparathyroidism, familial isolated |
| GDF9 | Premature ovarian failure 14 |
| GHR | Growth hormone insensitivity, partial; Laron dwarfism |
| GLIS3 | Diabetes mellitus, neonatal, with congenital hypothyroidism |
| GNAS | McCune-Albright syndrome; ACTH-independent macronodular adrenal hyperplasia; Pseudohypoparathyroidism Ia; Pseudohypoparathyroidism Ib; Pseudohypoparathyroidism Ic; Pseudopseudohypoparathyroidism; Osseous heteroplasia, progressive |
| GNRH1 | Hypogonadotropic hypogonadism 12 with or without anosmia |
| GNRHR | Hypogonadotropic hypogonadism 7 without anosmia |
| HARS2 | Perrault syndrome 2 |
| HESX1 | Growth hormone deficiency with pituitary anomalies |
| HFM1 | Premature ovarian failure 9 |
| HSD17B4 | Perrault syndrome 1 |
| HS6ST1 | Hypogonadotropic hypogonadism 15 with or without anosmia |
| IGSF1 | Hypothyroidism, central, and testicular enlargement |
| IL17RD | Hypogonadotropic hypogonadism 18 with or without anosmia |
| IRS4 | Hypothyroidism, congenital, nongoitrous, 9 |
| IYD | Thyroid dyshormonogenesis 4 |
| KISS1 | Hypogonadotropic hypogonadism 13 with or without anosmia |
| KISS1R | Hypogonadotropic hypogonadism 8 with or without anosmia; Precocious puberty, central, 1 |
| LARS2 | Perrault syndrome 4 |
| LHCGR | Leydig cell hypoplasia with hypergonadotropic hypogonadism |
| LHB | Isolated lutropin deficiency |
| LHX3 | Pituitary hormone deficiency, combined, 3 |
| LHX4 | Pituitary hormone deficiency, combined, 4 |
| MCM8 | Premature ovarian failure 10 |
| MCM9 | Ovarian dysgenesis 4 |
| MSH5 | Premature ovarian failure 13 |
| MRPS22 | Ovarian dysgenesis 7 |
| MTHFR | Homocystinuria due to MTHFR deficiency |
| NKX2-1 | Choreoathetosis, hypothyroidism, and neonatal respiratory distress |
| NKX2-5 | Hypothyroidism, congenital nongoitrous, 5 |
| NOBOX | Premature ovarian failure 5 |
| NR0B1 | Adrenal hypoplasia, congenital; 46XY sex reversal 2, dosage-sensitive |
| NR5A1 | Premature ovarian failure 7; 46, XX sex reversal 4; 46XY sex reversal 3 |
| NSMF | Hypogonadotropic hypogonadism 9 with or without anosmia |
| NUP107 | Ovarian dysgenesis 6; Nephrotic syndrome, type 11; Galloway-Mowat syndrome 7 |
| OTX2 | Pituitary hormone deficiency, combined, 6; Retinal dystrophy, early-onset, with or without pituitary dysfunction |
| PADI6 | Preimplantation embryonic lethality 2 |
| PATL2 | Oocyte maturation defect 4 |
| PAX8 | Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia |
| PDE3A | Hypertension and brachydactyly syndrome |
| POLR3B | Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism |
| POU1F1 | Pituitary hormone deficiency, combined, 1 |
| PROC | Thrombophilia due to protein C deficiency, autosomal dominant; Thrombophilia due to protein C deficiency, autosomal recessive |
| PROK2 | Hypogonadotropic hypogonadism 4 with or without anosmia |
| PROKR2 | Hypogonadotropic hypogonadism 3 with or without anosmia |
| PROP1 | Pituitary hormone deficiency, combined, 2 |
| PROS1 | Thrombophilia due to protein S deficiency, autosomal dominant; Thrombophilia due to protein S deficiency, autosomal recessive |
| PSMC3IP | Ovarian dysgenesis 3 |
| SECISBP2 | Thyroid hormone metabolism, abnormal |
| SEMA3A | Hypogonadotropic hypogonadism 16 with or without anosmia |
| SERPINC1 | Thrombophilia due to antithrombin III deficiency |
| SERPINE1 | Plasminogen activator inhibitor-1 deficiency |
| SLC26A4 | Deafness, autosomal recessive 4, with enlarged vestibular aqueduct; Pendred syndrome |
| SLC5A5 | Thyroid dyshormonogenesis 1 |
| SOHLH1 | Ovarian dysgenesis 5 |
| SOX10 | PCWH syndrome; Waardenburg syndrome, type 2E, with or without neurologic involvement; Waardenburg syndrome, type 4C |
| SOX2 | Microphthalmia, syndromic 3 |
| SOX3 | Mental retardation, X-linked, with isolated growth hormone deficiency; Panhypopituitarism, X-linked |
| SPRY4 | Hypogonadotropic hypogonadism 17 with or without anosmia |
| SRA1 | Hypogonadism with anosmia |
| STAG3 | Premature ovarian failure 8 |
| SYCE1 | Premature ovarian failure 12 |
| SYCP3 | Pregnancy loss, recurrent, 4 |
| TAC3 | Hypogonadotropic hypogonadism 10 with or without anosmia |
| TACR3 | Hypogonadotropic hypogonadism 11 with or without anosmia |
| TBL1X | Hypothyroidism, congenital, nongoitrous, 8 |
| TG | Thyroid dyshormonogenesis 3 |
| THBD | Thrombophilia due to thrombomodulin defect |
| THRA | Hypothyroidism, congenital, nongoitrous, 6 |
| THRB | Thyroid hormone resistance; Thyroid hormone resistance, autosomal recessive; Thyroid hormone resistance, selective pituitary |
| TPO | Thyroid dyshormonogenesis 2A |
| TRH | Thyrotropin-releasing hormone deficiency |
| TRHR | Hypothyroidism, congenital, nongoitrous, 7 |
| TSHB | Hypothyroidism, congenital, nongoitrous 4 |
| TSHR | Hyperthyroidism, familial gestational; Hypothyroidism, congenital, nongoitrous, 1 |
| TUBB8 | Oocyte maturation defect 2 |
| WDR11 | Hypogonadotropic hypogonadism 14 with or without anosmia |
| WEE2 | Oocyte maturation defect 5 |
| WNT4 | Mullerian aplasia and hyperandrogenism; SERKAL syndrome |
| WT1 | Frasier syndrome; Denys-Drash syndrome; Meacham syndrome |
| ZP1 | Oocyte maturation defect 1 |
| ZP2 | Oocyte maturation defect 6 |
| ZP3 | Oocyte maturation defect 3 |
Female Infertility NGS panel
Published 11/03/2020Female Infertility NGS panel
| Genes: | ANOS1, AR, AXL, BMP15, BMP4, CASR, CCDC141, CFTR, CLPP, CPEB1, DUOX1, DUOX2, DUOXA2, DUSP6, EIF2B1, EIF2B2, EIF2B4, EIF2B5, EIF4ENIF1, ERCC6, ESR1, ESR2, F2, F5, FEZF1, FGF17, FGF8, FGFR1, FIGLA, FLRT3, FMR1 (incl CGG trinucleotide repeat expansion), FOXE1, FOXL2, FSHB, FSHR, GCM2, GDF9, GHR, GLIS3, GNAS, GNRH1, GNRHR, HARS2, HESX1, HFM1, HSD17B4, HS6ST1, IGSF1, IL17RD, INHA, IRS4, IYD, KISS1, KISS1R, LARS2, LHCGR, LHB, LHX3, LHX4, LHX8, MCM8, MCM9, MRPS22, MSH5, MTHFR, NANOS3, NKX2-1, NKX2-5, NLRP2, NLRP5, NOBOX, NR0B1, NR5A1, NSMF, NUP107, OTX2, PADI6, PATL2, PAX8, PDE3A, PLCZ1, POLR3B, POU1F1, PROC, PROK2, PROKR2, PROP1, PROS1, PSMC3IP, SECISBP2, SEMA3A, SERPINC1, SERPINE1, SLC26A4, SLC5A5, SMC1B, SOHLH1, SOX10, SOX2, SOX3, SPIDR, SPRY4, SRA1, STAG3, SYCE1, SYCE3, SYCP3, TAC3, TACR3, TBL1X, TG, THBD, THRA, THRB, TPO, TRH, TRHR, TSHB, TSHR, TTF1, TUBB8, WDR11, WEE2, WNT4, WT1, ZP1, ZP2, ZP3 |
| Lab method: | NGS panel with CNV analysis |
| TAT: | 6-9 weeks |
| Specimen requirements: | 2-4 ml of blood with anticoagulant EDTA
1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl |
| Ordering information: | Go to online ordering or download sample submission form |
Indications for genetic testing:
- Suspected infertility in women who had already undergone basic clinical analysis and karyotype analysis
- Primary ovarian dysfunction or recurrent fetal loss
- Testing of infertile couples who will be undergoing treatment with assisted reproductive technology (ART), especially a genetic anomaly is found in either one component of the couple
- Evaluation of the risk of disease to be transmitted to the child to be born through ART
Female factors account for at least 35% of all infertility cases and comprise a wide range of causes affecting ovarian development, maturation of oocytes, and fertilization competence as well as the potential of a fertilized egg for preimplantation development, implantation, and fetal growth.
Other factors influencing female infertility include diseases such as polycystic ovarian syndrome (PCOS) and endometriosis, and the cumulative effects of environmental factors and lifestyle. PCOS, the most common cause of infertility is a complex, hormonal and metabolic disorder affecting 5–20% of women of reproductive age. The disease is characterised by hyperandrogenism, ovulatory dysfunction, polycystic ovarian morphology and gonadotropic abnormalities. Endometriosis affects 7–10% of women and is associated with infertility.
Genetic abnormalities leading to infertility in females encompass large chromosome abnormalities, submicroscopic chromosome deletion and duplications, and DNA sequence variations in the genes involved in oogenesis, maintenance of ovarian reserve, hormonal signaling, and anatomical and functional development of female reproductive organs. Genetic abnormalities are implicated in about 10% of female infertility cases.
References:
Dallel, M. et al 2018. Differential association of DENND1A genetic variants with polycystic ovary syndrome in Tunisian but not Bahraini Arab women. Gene 647, 79–84
Day, FR et al 2015. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat. Commun. 6, 8464.
Foresta, C 2002. Guidelines for the appropriate use of genetic tests in infertile couples. European Journal of Human Genetics, 10(5), 303–312.
Gajbhiye, R et al 2018. Complex genetics of female fertility. Npj Genomic Medicine, 3(1).
Giudice, LC and Kao, LC 2004. Endometriosis. Lancet 364, 1789–1799.
Azziz, R 2016. PCOS in 2015: New insights into the genetics of polycystic ovary syndrome. Nat. Rev. Endocrinol. 12, 183.
Lambalk, CB et al 2017. GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum Reprod.
Lawler, AM and Gearhart, JD 1998. Genetic counselling for patients who will be undergoing treatmnent with assisted reproductive technology. Fertil Steril 70: 412 ± 413.
Norman, RJ et al 2007. Polycystic ovary syndrome. Lancet 370, 685–697.
Venkatesh, T et al 2014. New insights into the genetic basis of infertility. Appl Clin Genet. 2014; 7: 235–243.
Yatsenko, SA and Rajkovic, A 2019. Genetics of human female infertility. Biol Reprod. 2019 Sep 1;101(3):549-566.