TABLE 2.
Variations found in individuals presenting with syndromic amelogenesis imperfecta.
| Patient number | Diagnosis/AI | Gene | Variant and location | Zygosity | Mode of inheritance | Rank | Effect of the mutation | Consistent with the known disease phenotype | Family segregation | Status |
|---|---|---|---|---|---|---|---|---|---|---|
| 17.1 (female) | Hypoplastic, short stature | LTBP3 Chr11 ( GRCh37 ) : NM_001130144.3 | c.421C>T; p.(Gln141*) Exon 2 Huckert M et al. (2015) | compound heterozygous | AR | 4 | non-sense | Yes | S(A,C) | exome |
| c.1531 + 1G>T; p.? Intron 8 Huckert M et al. (2015) | AR | 4 | splice | S(A,C) | ||||||
| 17.2 (female) | Hypoplastic, short stature | LTBP3 Chr11 ( GRCh37 ) : NM_001130144.3 | c.2071_2084del; p.(Tyr691Leufs*95) Exon 14 Huckert M et al. (2015) | homozygous | AR | 4 | frameshift | Yes | S(A,C) S(U,R) MoFa(U,C) | exome |
| 17.3 (male) | Hypoplastic, short stature | LTBP3 Chr11 ( GRCh37 ) : NM_001130144.3 | c.2216del; p.(Gly739Alafs*7) Exon 15 Huckert M et al. (2015) | homozygous | AR | 4 | frameshift | Yes | MoFa(U,C) | exome |
| 17.4 (male) | Hypoplastic, short stature | LTBP3 Chr11 ( GRCh37 ) : NM_001130144.3 | c.2356del; p.(Val786Trpfs*82) Exon 17 Huckert M et al. (2015) | homozygous | AR | 4 | frameshift | Yes | MoFa(U,C) 3S(A,C) | exome |
| 17.5 (female) | Hypoplastic, short stature | LTBP3 Chr11 ( GRCh37 ) : NM_001130144.3 | c.3087del; p.(Asn1030Thrfs*47) Exon 22 | homozygous | AR | 4 | frameshift | Yes | MoFa(U,C) | panel |
| 17.6 (female) | Hypoplastic, short stature | LTBP3 Chr11 ( GRCh37 ) : NM_001130144.3 | c.3629-2A>G; p.? Intron 26 | homozygous | AR | 4 | splice | Yes | MoFa(U,C) | panel |
| Patient number | Diagnosis/AI | Gene | Variant and location | Zygosity | Rank | Effect of the mutation | Consistent with the known disease phenotype | Family segregation | Status | |
| 18.1 (female) | Hypoplastic AI, nephrocalcinosis | FAM20A Chr17(GRCh37): NM_017565.4 | c.34_35del; p.(Leu12Alafs*67) Exon 1 Cho et al. (2012) | compound heterozygous | AR | 5 | frameshift | Yes | S(A,C) | panel |
| c.610del; p.(Ala204Profs*12) Exon 3 | AR | 4 | frameshift | S(A,C) | ||||||
| 18.2 (male) | Hypoplastic AI, nephrocalcinosis | FAM20A Chr17(GRCh37): NM_017565.4 | c.53_54delinsAG; p.(Leu18Arg) Exon 1 | putative compound heterozygous | AR | 3 | missense | Yes | NA | panel |
| c.976_978del; p.(Glu326del) Exon 7 | AR | 3 | deletion | NA | ||||||
| 18.3 (male) | Hypoplastic AI, nephrocalcinosis | FAM20A Chr17(GRCh37): NM_017565.4 | c.217C>T; p.(Arg73*) Exon 1 Jaureguiberry et al. (2012) | compound heterozygous | AR | 4 | non-sense | Yes | Fa(U,C) S(A,C) | exome |
| c.727C>T; p.(Arg243*) Exon 5 Jaureguiberry et al. (2012) | AR | 4 | non-sense | Mo(U,C) S(A,C) | ||||||
| 18.4 (female) | Hypoplastic AI, nephrocalcinosis | FAM20A Chr17(GRCh37): NM_017565.4 | c.406C>T; p.(Arg136*) Exon 2 O'Sullivan et al. (2011) | homozygous | AR | 5 | non-sense | Yes | NA | panel |
| 18.5 (male) | Hypoplastic AI, nephrocalcinosis | FAM20A Chr17(GRCh37): NM_017565.4 | c.915_918del; p.(Phe305Leufs*76) Exon 6 Jaureguiberry et al. (2012) | compound heterozygous | AR | 4 | frameshift | Yes | Fa(U,C) | panel |
| c.928 + 2T>C; p.? Intron 6 | AR | 4 | splice | Mo(U,C) | ||||||
| 18.6 (male) | Hypoplastic AI, nephrocalcinosis | FAM20A Chr17(GRCh37): NM_017565.4 | c.915_918del; p.(Phe305Leufs*76) Exon 6 Jaureguiberry et al. (2012) | compound heterozygous | AR | 4 | frameshift | Yes | S(A,C) Mo(U,C) | panel |
| FAM20A Chr17(GRCh37): NM_017565.4 | c.1301 + 5G>A; p.? Intron 9 | AR | 3 | splice | Yes | S(A,C) Fa(U,C) | panel | |||
| 18.7 (female) | Hypoplastic AI, nephrocalcinosis | FAM20A Chr17(GRCh37): NM_017565.4 | c.1106_1107delAG; p.(Glu369Glyfs*10) Exon 7 Prasad et al. (2016a) | homozygous | AR | 4 | frameshift | Yes | NA | panel |
| 18.8 (female) | Hypoplastic AI, nephrocalcinosis | FAM20A Chr17(GRCh37): NM_017565.4 | c.1361 + 1G>A; p.? Intron 10 | homozygous | AR | 4 | splice | Yes | NA | exome |
| 18.9 (female) | Hypoplastic AI, nephrocalcinosis | FAM20A Chr17(GRCh37): NM_017565.4 | c.1369A>T; p.(Lys457*) Exon 11 Jaureguiberry et al. (2012) | homozygous | AR | 4 | non-sense | Yes | S(A,C) | panel |
| 18.10 (female) | Hypoplastic AI, nephrocalcinosis | FAM20A Chr17(GRCh37): NM_017565.4 | c.1369A>T; p.(Lys457*) Exon 11 Jaureguiberry et al. (2012) | homozygous | AR | 4 | non-sense | Yes | MoFa(U,C) | exome |
| Patient number | Diagnosis/AI | Gene | Variant and location | Zygosity | Rank | Effect of the mutation | Consistent with the known disease phenotype | Family segregation | Status | |
| 19.1 (male) | Hypoplastic, pits, mucopolysaccharidosis IV | GALNS Chr16(GRCh37):NM_000512.5 | c.121-31T>C; p.? Intron 1 Prasad et al. (2016b) | compound heterozygous | AR | 3 | splice | Yes | Mo(U,C) | panel |
| c.953C>G; p.(Thr312Ser) Exon 9 Yamada et al. (1998) | AR | 5 | missense | Fa(U,C) | ||||||
| 19.2 (female) | Hypoplastic, pits, mucopolysaccharidosis IV | GALNS Chr16 ( GRCh37 ) : NM_000512.5 | c.1156C>T; p.(Arg386Cys) Exon 11 Ogawa et al. (1995) | heterozygous | AR | 5 | missense | Yes | Mo(U,R) Fa(U,R) | panel |
| c.1558T>C; p.(Trp520Arg) Exon 14 Zanetti et al. (2021) | heterozygous | AR | 2 | missense | M(U,Chom) | |||||
| Patient number | Diagnosis/AI | Gene | Variant and location | Zygosity | Rank | Effect of the mutation | Consistent with the known disease phenotype | Family segregation | Status | |
| 20.1 (female) | Hypoplastic, banding pattern, Lyonisation, Microphthalmia with linear skin defects (MLS) syndrome | AMELX-ARHGAP6 ChrX ( GRCh37 ) :g.125958-12725766del | ChrX(GRCh37):g.125958-12725766del Many genes including AMELX | heterozygous | XL | 4 | deletion | Yes | NA | panel |
| Patient number | Diagnosis/AI | Gene | Variant and location | Zygosity | Rank | Effect of the mutation | Consistent with the known disease phenotype | Family segregation | Status | |
| 21.1 (male) | Hypoplastic, Smith Magenis syndrome | RAI1 | arr[GRCh37] 17p11.2(17280004_20239827)x1 Many genes including RAI1 | heterozygous | AD | 4 | deletion | - | NA | panel |
| Patient number | Diagnosis/AI | Gene | Variant and location | Zygosity | Rank | Effect of the mutation | Consistent with the known disease phenotype | Family segregation | Status | |
| 22.1 (male) | Hypoplastic, Loeys-Dietz syndrome | TGFBR2 Chr4(GRCh37): NM_003242.6 | c.1561T>C; p.(Trp521Arg) Exon 7 Mátyás et al. (2006) | heterozygous | AD | 5 | missense | Yes | Fa(U,R) Mo(A,NA) | panel |
| Patient number | Diagnosis/AI | Gene | Variant and location | Zygosity | Rank | Effect of the mutation | Consistent with the known disease phenotype | Family segregation | Status | |
| 23.1 (female) | Hypoplastic, Kohlschutter-Tonz like syndrome | SLC13A5 Chr17(GRCh37): NM_177550.5 | c.203C>A; p.(Pro68Gln) Exon 2 Schossig et al. (2017) | compound heterozygous | AR | 4 | missense | Yes | S(A,C) | panel |
| c.434C>A; p.(Thr145Lys) Exon 4 Schossig et al. (2017) | AR | 4 | missense | S(A,C) | ||||||
| Patient number | Diagnosis/AI | Gene | Variant and location | Zygosity | Rank | Effect of the mutation | Consistent with the known disease phenotype | Family segregation | Status | |
| 24.1 (female) | Hypomature, Kohlschutter Tonz syndrome | ROGDI Chr16 ( GRCh37 ) : NM_024589.3 | c.46 + 37_46-30del; p.? Intron 1 Tucci et al. (2013) | compound heterozygous | AR | 4 | deletion | Yes | Mo(U,C) | Insbruck |
| c.507del; p.(Glu170Argfs*72) Exon 7 Tucci et al. (2013) | AR | 4 | deletion | Fa(U,C) | ||||||
| 24.2 (female) | Hypomature, Kohlschutter Tonz syndrome | ROGDI Chr16 ( GRCh37 ) : NM_024589.3 | c.117 + 1G>T; p.? Intron 2 Huckert et al. (2014) | homozygous | AR | 4 | splice | Yes | NA | panel |
| 24.3 (female) | Hypomature, Kohlschutter Tonz syndrome | ROGDI Chr16 ( GRCh37 ) : NM_024589.2 | c.366dup; p.(Ala123Serfs*19) Exon 6 Tucci et al. (2013) | compound heterozygous | AR | 4 | frameshift | Yes | Mo(U,C) | panel |
| c.402C>G; p.(Tyr134*) Exon 6 Aswath al. (2018) | AR | 4 | non-sense | Fa(U,C) | ||||||
| Patient number | Diagnosis/AI | Gene | Variant and location | Zygosity | Rank | Effect of the mutation | Consistent with the known disease phenotype | Family segregation | Status | |
| 25.1 (male) | Hypomature/Hypomineralized, short stature, intra-uterine growth retardation, skeletal dysplasia, submucosal cleft palate | SLC10A7 Chr4(GRCh37): NM_001300842.3 | c.269T>G; p.(Leu90Arg) Exon 3 | homozygous | AR | 3 | missense | Yes | MoFa(U,C) | panel |
| 25.2 (female) | Hypomature/Hypomineralized, short stature, intra-uterine growth retardation, skeletal dysplasia | SLC10A7 Chr4(GRCh37): NM_001300842.3 | c.908C>T; p.(Pro303Leu) Exon 11 Laugel-Haushalter et al. (2019) | homozygous | AR | 4 | missense | Yes | MoFa3S(U,C) | exome |
| Patient number | Diagnosis/AI | Gene | Variant and location | Zygosity | Rank | Effect of the mutation | Consistent with the known disease phenotype | Family segregation | Status | |
| 26.1 (female) | Hypomineralized, Jalili syndrome | CNNM4 Chr2 ( GRCh37 ) : NM_020184.4 | c.586T>C; p.(Ser196Pro) Exon 1 Parry et al. (2009) | homozygous | AR | 4 | missense | Yes | S(A,C) Mo(U,C) | panel |
| 26.2 (male) | Hypomineralized, Jalili syndrome | CNNM4 Chr2 ( GRCh37 ) : NM_020184.4 | c.1495G>A; p.(Val499Met) Exon 2 Prasad MK et al. (2016b) | homozygous | AR | 4 | missense | Yes | NA | panel |
| Patient number | Diagnosis/AI | Gene | Variant and location | Zygosity | Rank | Effect of the mutation | Consistent with the known disease phenotype | Family segregation | Status | |
| 27.1 (female) | Hypoplastic, Trichodentoosseus syndrome | DLX3 Chr17 ( GRCh37 ) : NM_005220.3 | c.561_562del; p.(Tyr188Glnfs*13) Exon 3 Dong et al. (2005) | heterozygous | AD | 4 | frameshift | Yes | MoS(A,C) | panel |
| 27.2 (male) | Hypoplastic, Trichodentoosseus syndrome | DLX3 Chr17 ( GRCh37 ) : NM_005220.3 | c.561_562del; p.(Tyr188Glnfs*13) Exon 3 Dong et al. (2005) | heterozygous | AD | 4 | frameshift | Yes | Fa(A,C) | panel |
Variations found in 11 different genes in 31 individuals presenting with syndromic amelogenesis imperfecta. Forty-two variants were found, 7 variants are of uncertain significance.
Variants known before the panel implementation are reported in grey, variants previously reported by the team are represented in salmon, variants published thanks to the panel are represented in blue or green, variants reported for the first time are highlighted in green. Familial segregation is also reported when available and reported in this format: Family member code (Phenotype code, Genotype code). Fa: father; Mo: mother; S: sibling; D: daughter; So: son; Co: cousin; A: affected; U: unaffected; NA: not available; C: carrier; R: reference genotype.