Illness46XX infertility / sterility, differential diagnosis

NGS +

[Sanger]

Infertility is defined as a disease of the reproductive system characterized by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse (WHO-ICMART). Accordingly, approximately 10% of women of reproductive age are unable to become pregnant or carry a pregnancy to term. Female factors alone account for at least one-third of all infertility cases and include a wide range of causes that affect ovarian development, oocyte maturation and fertilization competence as well as the potential of a fertilized oocyte for preimplantation development, implantation and fetal growth. Genetic abnormalities leading to infertility in women include chromosomal abnormalities, submicroscopic chromosomal deletions/duplications and DNA sequence variations in the many genes that control numerous biological processes involved in oogenesis, maintenance of ovarian reserve, hormonal signaling, anatomical and functional development of the female reproductive organs. The following genetic entities of disorders are included that are recurrent in infertility: Mosaic variegated aneuploidy syndrome, Mullerian aplasia in hyperandrogenism, oocyte maturation defects, ovarian dysgenesis, ovarian hyperstimulation syndrome, ovarian response to FSH stimulation, pregnancy loss, recurrent preimplantation embryo lethality, premature chromatid separation, premature ovarian failure and primary ovarian insufficiency. Yet, because very many cases of infertility are multifactorial, the molecular genetic yield is not precisely definable. An inconspicuous genetic finding does not mean exclusion of the suspected clinical diagnosis.

Reference: https://doi.org/10.1093/biolre/ioz084

• Allelic: 46XX sex reversal 4 (NR5A1)
• Allelic: 46XY sex reversal 2, dosage-sensitive (NR0B1)
• Allelic: 46XY sex reversal 3 (NR5A1)
• Allelic: Acromesomelic dysplasia, Demirhan type (BMPR1B)
• Allelic: Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency (CYP21A2)
• Allelic: Adrenocortical insufficiency (NR5A1)
• Allelic: Brachydactyly, type A1, D (BMPR1B)
• Allelic: Brachydactyly, type A2 (BMPR1B)
• Allelic: Breast cancer, somatic (ESR1)
• Allelic: Budd-Chiari syndrome (F5)
• Allelic: Cerebrooculofacioskeletal syndrome 1 (ERCC6)
• Allelic: Cockayne syndrome, type B (ERCC6)
• Allelic: Colorectal cancer, somatic (BUB1B)
• Allelic: Combined oxidative phosphorylation deficiency 5 (MRPS22)
• Allelic: Congenital bilateral absence of vas deferens (CFTR)
• Allelic: Cystic fibrosis (CFTR)
• Allelic: De Sanctis-Cacchione syndrome (ERCC6)
• Allelic: Dysprothrombinemia (F2)
• Allelic: Factor V deficiency (F5)
• Allelic: Fragile X syndrome (FMR1 repeat)
• Allelic: Fragile X tremor/ataxia syndrome (FMR1 repeat)
• Allelic: Galloway-Mowat syndrome 7 (NUP107)
• Allelic: Holoprosencephaly 9 (GLI2)
• Allelic: Hypertrypsinemia, neonatal (CFTR)
• Allelic: Hypoprothrombinemia (F2)
• Allelic: Hypospadias 1, X-linked (AR)
• Allelic: IVIC syndrome (SALL4)
• Allelic: Leydig cell adenoma, somatic, with precocious puberty (LHCGR)
• Allelic: Leydig cell hypoplasia with hypergonadotropic hypogonadism (LHCGR)
• Allelic: Leydig cell hypoplasia with pseudohermaphroditism (LHCGR)
• Allelic: Lung cancer, susceptibility to (ERCC6)
• Allelic: Macular degeneration, age-related, susceptibility to, 5 (ERCC6)
• Allelic: Migraine, susceptibility to (ESR1)
• Allelic: Multiple fibroadenomas of the breast (PRLR)
• Allelic: Myocardial infarction, susceptibility to (ESR1)
• Allelic: Nephrotic syndrome, type 11 (NUP107)
• Allelic: Neutropenia, severe congenital 3, AR (HAX1)
• Allelic: PCWH syndrome (SOX10)
• Allelic: Pancreatitis, hereditary (CFTR)
• Allelic: Precocious puberty, male (LHCGR)
• Allelic: Prostate cancer, susceptibility to (AR)
• Allelic: SERKAL syndrome (WNT4)
• Allelic: Spermatogenic failure 32 (SOHLH1)
• Allelic: Spermatogenic failure 4 (SYCP3)
• Allelic: Spermatogenic failure 8 (NR5A1)
• Allelic: Spinal + bulbar muscular atrophy of Kennedy (AR repeat)
• Allelic: Stroke, ischemic, susceptibility to (F2, F5)
• Allelic: Sweat chloride elevation without CF (CFTR)
• Allelic: Thrombophilia due to activated protein C resistance (F5)
• Allelic: Thrombophilia due to thrombin defect (F2)
• Allelic: Thrombophilia, susceptibility to, due to factor V Leiden (F5)
• Allelic: UV-sensitive syndrome (ERCC6)
• Allelic: Waardenburg syndrome, type 2E, with/-out neurologic involvement (SOX10)
• Allelic: Waardenburg syndrome, type 4C (SOX10)
• "Fertility stabilizer" (PGRMC1)
• Adrenal hypoplasia, congenital (NR0B1)
• Androgen insensitivity (AR)
• Androgen insensitivity, partial, with/-out breast cancer (AR)
• Bronchiectasis with/-out elevated sweat chloride 1, modifier of (CFTR)
• Culler-Jones syndrome (GLI2)
• Duane-radial ray syndrome (SALL4)
• Estrogen resistance (ESR1)
• Galactosemia (GALT)
• Growth hormone deficiency with pituitary anomalies (HESX1)
• Hydatidiform mole, recurrent, 1 (NLRP7)
• Hydatidiform mole, recurrent, 2 (KHDC3L)
• Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency (CYP21A2)
• Hyperprolactinemia (PRLR)
• Hypogonadotropic hypogonadism 1 with/-out anosmia; Kallmann syndrome 1 (ANOS1)
• Hypogonadotropic hypogonadism 10 with/-out anosmia (TAC3)
• Hypogonadotropic hypogonadism 11 with/-out anosmia (TACR3)
• Hypogonadotropic hypogonadism 12 with/-out anosmia (GNRH1)
• Hypogonadotropic hypogonadism 13 with/-out anosmia (KISS1)
• Hypogonadotropic hypogonadism 14 with/-out anosmia (WDR11)
• Hypogonadotropic hypogonadism 15 with or without anosmia (HS6ST1)
• Hypogonadotropic hypogonadism 16 with/-out anosmia (SEMA3A)
• Hypogonadotropic hypogonadism 17 with/-out anosmia (SPRY4)
• Hypogonadotropic hypogonadism 19 with/-out anosmia (DUSP6)
• Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Hypogonadotropic hypogonadism 20 with/-out anosmia (FGF17)
• Hypogonadotropic hypogonadism 21 with anosmia (FLRT3)
• Hypogonadotropic hypogonadism 22, with/-out anosmia (FEZF1)
• 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 5 with/-out anosmia (CHD7)
• Hypogonadotropic hypogonadism 6 with/-out anosmia (FGF8)
• Hypogonadotropic hypogonadism 7 without anosmia (GNRHR)
• Hypogonadotropic hypogonadism 8 with/-out anosmia (KISS1R)
• Hypogonadotropic hypogonadism 9 with/-out anosmia (NSMF)
• Luteinizing hormone resistance, female (LHCGR)
• Mosaic variegated aneuploidy syndrome 1 (BUB1B)
• Mosaic variegated aneuploidy syndrome 3 (TRIP13)
• Mullerian aplasia + hyperandrogenism (WNT4)
• Obesity, morbid, due to leptin deficiency (LEP)
• Obesity, morbid, due to leptin receptor deficiency (LEPR)
• Oocyte maturation defect 1 (ZP1)
• Oocyte maturation defect 9 (TRIP13)
• Ovarian dysgenesis 1 (FSHR)
• Ovarian dysgenesis 2 (BMP15)
• Ovarian dysgenesis 3 (PSMC3IP)
• Ovarian dysgenesis 4 (MCM9)
• Ovarian dysgenesis 5 (SOHLH1)
• Ovarian dysgenesis 6 (NUP107)
• Ovarian dysgenesis 7 (MRPS22)
• Ovarian dysgenesis 8 (ESR2)
• Ovarian hyperstimulation syndrome (FSHR)
• Ovarian response to FSH stimulation (FSHR)
• Pituitary hormone deficiency, combined, 2 (PROP1)
• Pituitary hormone deficiency, combined, 5 (HESX1)
• Pregnancy loss, recurrent, 4 (SYCP3)
• Pregnancy loss, recurrent, susceptibility to, 1 (F5)
• Pregnancy loss, recurrent, susceptibility to, 2 (F2)
• Pregnancy loss, recurrent, susceptibility to, 3 (ANXA5)
• Preimplantation embryonic lethality (TLE6)
• Preimplantation embryonic lethality 2 (PADI6)
• Premature chromatid separation trait (BUB1B)
• Premature ovarian failure 1 (FMR1 repeat)
• Premature ovarian failure 10 (MCM8)
• Premature ovarian failure 11 (ERCC6)
• Premature ovarian failure 13 (MSH5)
• Premature ovarian failure 14 (GDF9)
• Premature ovarian failure 2A (DIAPH2)
• Premature ovarian failure 2B (POF1B)
• Premature ovarian failure 3 (FOXL2)
• Premature ovarian failure 4 (BMP15)
• Premature ovarian failure 5 (NOBOX)
• Premature ovarian failure 6 (FIGLA)
• Premature ovarian failure 7 (NR5A1)
• Premature ovarian failure 8 (STAG3)
• Premature ovarian failure 9 (HFM1)
• Primary ovarian insufficiency (SOHLH2)
• Primary ovarian insufficiency (SOX8)
• Primary ovarian insufficiency [panelapp] (SOHLH2)
• Rickets, vitamin D-resistant, type IIA (VDR)
• Septooptic dysplasia (HESX1)
• Spermatogenic failure, XL, 2 (TEX11)