Congenital adrenal hyperplasia
At a minimum, these SNPs are known to be related, and others may also be
| Max Magnitude | |
|---|---|
| rs104894069 | 0 |
| rs104894070 | 0 |
| rs1819698 | 0 |
| rs193922538 | 0 |
| rs193922539 | 0 |
| rs193922540 | 0 |
| rs193922541 | 0 |
| rs556794126 | 0 |
| rs6162 | 0 |
| rs61752786 | 0 |
| rs6387 | 0 |
| rs6410 | 0 |
| rs6472 | 0 |
| rs743572 | 0 |
Congenital adrenal hyperplasia (CAH) are any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands (steroidogenesis); several such genes are listed in the table below. Most of these conditions involve excessive or deficient production of sex steroids and can alter development of primary or secondary sex characteristics in some affected infants, children, or adults.[1]
| Common medical term | % | OMIM | "'Gene"' | Enzyme(s) |
|---|---|---|---|---|
| 21-hydroxylase CAH | 90-95% | 201910 | CYP21A2 | P450c21 |
| 11β-hydroxylase CAH | 5% | 202010 | CYP11B1 | P450c11β |
| 3β-HSD CAH | very rare | 201810 | HSD3B2 | 3βHSD II |
| 17α-hydroxylase CAH | very rare | 202110 | CYP17A1 | P450c17 |
| lipoid CAH (20,22-desmolase) |
very rare | 201710 | STAR | StAR P450scc |
23andMe has a high rate of miscalls for SNPs in the CYP21A2 gene. Examples include
This is presumably due to the presence of a nearby CYP21 pseudogene as documented in omim
The most common forms of CAH arise from mutations in the CYP21A2 gene on chromosome 6. This gene encodes steroid 21-hydroxylase, so the corresponding disorder is also commonly known as 21-hydroxylase deficiency. There are at least four recognized clinical forms of congenital adrenal hyperplasia: salt-wasting, simple virilizing (SV) or classic, nonclassic (NC) or late-onset, and cryptic. In some cases a single mutation leads to a single recognized clinical form, but in many cases there are multiple mutations on the same allele, as well as high inter-individual variability.
In terms of prevalence, congenital adrenal hyperplasia is not that rare of a recessive disease type; it is estimated to affect 1/15,000 births, and 1 in 60 individuals are estimated to be (unaffected) carriers of a pathogenic variant.
The following table summarizes the SNPs and their phenotypes; the allele designations are taken from the CYP21A2 Allele table at the Human Cytochrome P450 (CYP) Allele Nomenclature Database. Note that the 'change' indicated is oriented to the forward/plus/cDNA strand, regardless of which strand the dbSNP (or SNPedia) SNP is defined as being on.
| Rsid | Change | Allele name | Synonym | Clinical type | OMIM | Clinvar significance | GRCh37 position, ch 6 | i-id (23andMe) | On chip? |
|---|---|---|---|---|---|---|---|---|---|
| rs151344503 | G>A | CYP21A2*27 | Trp406Ter | salt-wasting | 613815.0022 | pathogenic | 32008543 | i5005427 | Ancestry v2c, Ancestry v2d 23andMe v4, 23andMe v3 |
| rs201552310 | G>A | CYP21A2*171 | Gly292Ser | salt-wasting | 613815.0007 | pathogenic | 32007917 | ||
| rs267606756 | (- > T) | 613815.0033 | pathogenic | 32007964 | |||||
| rs267606757 | A>C | CYP21A2*151 | Lys121Gln | 613815.0035 | 32006939 | Ancestry v2c, Ancestry v2d | |||
| rs387906510 | delGAGACTAC | CYP21A2*10 | 8bp del | salt-wasting | 613815.0015 | pathogenic | 32006910 - 32006917 | Ancestry v2, Ancestry v2c, Ancestry v2d | |
| rs397509367 | GG>C | CYP21A2*25 | Arg484Fs | classic | 613815.0008 | pathogenic | 32008874 - 32008875 | ||
| rs6445 | C>T | CYP21A2*19 | Pro453Ser | nonclassic | 613815.0010 | pathogenic | 32008783 | 23andMe v4, Ancestry v2c, Ancestry v2d | |
| rs6467 | C>G or A>G | CYP21A2*9 | 613815.0006 | pathogenic | 32006858 | Ancestry v2c, FTDNA2, HumanOmni1Quad, Illumina Human 1M, Ancestry v2d | |||
| rs6471 | G>C | CYP21A2*15 | Val281Leu | nonclassic | 613815.0002 | pathogenic | 32007887 | ||
| rs6472 | G>C | CYP21A2*5 | Ser268Thr | benign variant | 613815.0005 | benign | 32007849 | 23andMe v4, 23andMe v3, 23andMe v2 | |
| rs6475 | T>A | CYP21A2*11 | Ile172Asn | classic | 613815.0001 | pathogenic | 32007203 | ||
| rs6476 | T>A | CYP21A2*14 | Met239Lys | salt-wasting | 613815.0016 | pathogenic | 32007593 | Ancestry v2, 23andMe v3, Ancestry v2d | |
| rs7755898 | C>T | CYP21A2*17 | Gln318Ter | salt-wasting | 613815.0020 | Pathogenic | 32008198 | ||
| rs7769409 | C>T | CYP21A2*18 | Arg356Trp | classic | 613815.0003 | 32008312 | i5005436 | 23andMe v4, 23andMe v3 | |
| rs9378251 | C>T | CYP21A2*8 | Pro30Leu | nonclassic | 613815.0004 | Pathogenic | 32006291 | ||
| rs151344504 | G>A | CYP21A2*82 | Arg426His | classic | 613815.0026 | 32008703 | i5005431 | 23andMe v4, 23andMe v3 | |
| rs151344505 | G>A | CYP21A2*71 | Val304Met | hyperandrogenism | 613815.0031 | 32007956 | i5005433 | 23andMe v4, 23andMe v3 | |
| rs151344506 | G>A | CYP21A2*72 | Gly375Ser | hyperandrogenism | 613815.0032 | 32008452 | i5005434 | 23andMe v4, 23andMe v3 | |
| rs397515532 | (- > T) | CYP21A2*16 | insT; Leu308PheFs | Pathogenic | 32007960-66 | ||||
| rs72552754 | G>A | CYP21A2*24 | Arg339His | nonclassic | 613815.0021 | Pathogenic | 32008262 | i5005425 | 23andMe v4, 23andMe v3 |
| rs72552756 | G>C | CYP21A2*35 | Glu380Asp | salt-wasting | 613815.0023 | 32008469 | |||
| rs72552757 | C>T | CYP21A2*73 | Arg408Cys | classic | 613815.0030 | 32008648 | i5005432 | 23andMe v4, 23andMe v3 | |
| rs72552758 | G>A | CYP21A2*55 | Gly424Ser | classic | 613815.0025 | 32008696 | i5005430 | 23andMe v4, 23andMe v3 | |
| rs9378252 | A>T | CYP21A2*91 | His62Leu | nonclassic | 613815.0034 | Pathogenic | 32006387 | i5005437 | 23andMe v3 23andMe v4, 23andMe v3 |
