Table 1.
Clinical and DNA sequence findings in 40 probands with AIRE mutations.
| Proband | Age (years)a | Clinical featuresc | Nucleotide changed,e | Predicted amino acid changee | Exon/intron |
|---|---|---|---|---|---|
| 1 | 23 | H, C, AH, V, E, P | c.1A>G(;)(1A>G)h | p.(Met1?)(;)(Met1?)f | Exon 1 |
| 2 | 9 | Hj | c.41A>C(;)(41A>C)g,h,i | p.(His14Pro)(;)(His14Pro) | Exon 1 |
| 3 | 14 | H, C, AD, T | c.44G>A(;)(44G>A)h | p.(Arg15His)(;)(Arg15His) | Exon 1 |
| 4 | 8b | APECED | c.83T>Ck | p.(Leu28Pro)k | Exon 1 |
| 5 | 9b | H, AD, DM | c.[242T>C];[1265delC] | p.[(Leu81Pro)];[(Pro422fs)] | Exon 2; Exon 10 |
| 6 | 13 | C, AD, AL | c.260delT(;)(260delT)h | p.(Leu87fs)(;)(Leu87fs) | Exon 2 |
| 7 | 17 | H, C | c.260delT(;)(260delT)h | p.(Leu87fs)(;)(Leu87fs) | Exon 2 |
| 8 | 11 | Hj | c.260delT(;)(260delT)h | p.(Leu87fs)(;)(Leu87fs) | Exon 2 |
| 9 | 17 | H, C | c.308-1G>C(;)(308-1G>C)l | - f | Intron 2 |
| 10 | 11 | H, AD, PO | c.[415C>T];[967_979del13] | p.[(Arg139Ter)];[(Leu323fs)] | Exon 3, Exon 8 |
| 11 | 10 | - m | c.463+2T>C(;)(463+2T>C)g,h,l | - f | Intron 3 |
| 12 | 12 | Hn | c.463+2T>Cg,l (;)967_979del13h | (- f)(;) p.(Leu323fs) | Intron 3; Exon 8 |
| 13 | 12 | Hj | c.607C>T(;)(607C>T)h | p.(Arg203Ter)(;)(Arg203Ter) | Exon 5 |
| 14 | 10 | - m | c.769C>T(;)(769C>T)h | p.(Arg257Ter)(;)(Arg257Ter) | Exon 6 |
| 15 | 19 | H, ND, EH, AL, TN | c.769C>T(;)967_979del13h | p.(Arg257Ter)(;)(Leu323fs) | Exon 6; Exon 8 |
| 16 | 5 | Hn | c.769C>T(;)967_979del13h | p.(Arg257Ter)(;)(Leu323fs) | Exon 6; Exon 8 |
| 17 | 17 | - m | c.[906T>A];[995+3_995+5delinsTAT]g,l | p.[Cys302Ter]; - f | Exon 8; Intron 9 |
| 18 | 49 | C | c.[913G>A]g;[967_979del13] | p.[(Gly305Ser)];[(Leu323fs)] | Exon 8 |
| 19 | 6b | H, AD, EH | c.967_979del13o | p.(Leu323fs) | Exon 8 |
| 20 | 4 | - m | c.967_979del13(;)(967_979del13)h | p.(Leu323fs)(;)(Leu323fs) | Exon 8 |
| 21 | 9 | - m | c.967_979del13(;)(967_979del13)h | p.(Leu323fs)(;)(Leu323fs) | Exon 8 |
| 22 | 11 | H, AD | c.[967_979del13];[967_979del13] | p.[(Leu323fs)];[(Leu323fs)] | Exon 8 |
| 23 | 53 | APECED | c.967_979del13(;)(967_979del13)h | p.(Leu323fs)(;)(Leu323fs) | Exon 8 |
| 24 | 5 | - m | c.967_979del13(;)(967_979del13)h | p.(Leu323fs)(;)(Leu323fs) | Exon 8 |
| 25 | 11 | Hj | c.[967_979del13];[967_979del13] | p.[(Leu323fs)];[(Leu323fs)] | Exon 8 |
| 26 | 39 | H, C, AD | c.967_979del13(;)(967_979del13)h | p.(Leu323fs)(;)(Leu323fs) | Exon 8 |
| 27 | 2 | Hn | c.[967_979del13];[967_979del13] | p.[(Leu323fs)];[(Leu323fs)] | Exon 8 |
| 28 | 62 | H, AD, T, PO | c.967_979del13(;)(967_979del13)h | p.(Leu323fs)(;)(Leu323fs) | Exon 8 |
| 29 | 10b | H, AD | c.967_979del13(;)(967_979del13)h | p.(Leu323fs)(;)(Leu323fs) | Exon 8 |
| 30 | 3 | H, C | c.[967_979del13];[967_979del13] | p.[(Leu323fs)];[(Leu323fs)] | Exon 8 |
| 31 | 16 | Hj | c.967_979del13(;)(967_979del13)h | p.(Leu323fs)(;)(Leu323fs) | Exon 8 |
| 32 | 4b | Hn | c.[967_979del13];[967_979del13] | p.[(Leu323fs)];[(Leu323fs)] | Exon 8 |
| 33 | 5b | H, AD | c.[967_979del13];[1265delC] | p.[(Leu323fs)];[(Pro422fs)] | Exon 8; Exon 10 |
| 34 | 9 | - m | c.967_979del13(;)1295_1296insAh | p.(Leu323fs)(;)(Arg433fs) | Exon 8; Exon 11 |
| 35 | 18 | H, AH | c.967_979del13(;)1347C>Ah | p.(Leu323fs)(;)(Cys449Ter) | Exon 8; Exon 11 |
| 36 | 14 | - m | c.1249dupC(;)(1249dupC)h | p.(Leu417fs)(;)(Leu417fs) | Exon 10 |
| 37 | 9 | Hn | c.[1249dupC];[1249dupC] | p.[(Leu417fs)];[(Leu417fs)] | Exon 10 |
| 38 | 33 | - m | c.1249dupC(;)(1249dupC)h | p.(Leu417fs)(;)(Leu417fs) | Exon 10 |
| 39 | 6 | - m | c.[1517delG];[1517delG] | p.[(Ser506fs)];[(Ser506fs)] | Exon 13 |
| 40 | 7 | Hn | c.[1517delG];[1517delG] | p.[(Ser506fs)];[(Ser506fs)] | Exon 13 |
aAge at the time of referral. bAge at initial presentation or diagnosis. cClinical features: H, hypoparathyroidism; C, candidiasis; AH; autoimmune hepatitis; V, vitiligo; E, enteropathy; P, pancreatic insufficiency; AD, adrenal insufficiency; T, hypothyroidism; DM, type 1 diabetes; AL, alopecia; EH, enamel hypoplasia; ND, nail dystrophy; TN, tubulointerstitial nephritis; PO, premature ovarian failure; APECED, reported to have clinical features of APECED syndrome. dNucleotides are numbered according to the AIRE cDNA reference sequence (NM_000383.3). eNucleotide and amino acid changes have been described according to Human Genome Variation Society nomenclature guidelines (http://varnomen.hgvs.org). Use of parentheses around the amino acid change indicates that this is a prediction based on the nucleotide substitution. Where variants are confirmed to be on different alleles (in trans), by family studies, the alleles are described in square brackets separated by a semicolon. Absence of square brackets and use of a semicolon in parentheses indicates prediction of in trans variants. Use of parentheses around the second allele in the nucleotide description indicates prediction of homozygosity (family studies not available to confirm). fThe effect of the variant at the protein level cannot be predicted. gVariant classified as likely pathogenic (class 4 variant). hHomozygosity or compound heterozygosity is assumed in the proband based on their genotype and phenotype, as family studies were not possible. iNovel variant. jMutation or variant identified from analysis of hypoparathyroidism genes rather than from isolated AIRE analysis. kCompound heterozygous mutation with unbalanced translocation resulting in monosomy for AIRE, and a missense substitution affecting the remaining AIRE allele. lIntronic variant predicted to affect splicing efficiency. m-, not available. nClinical details incomplete. oMutation associated with uniparental isodisomy.
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