Table 1.
Summary of the variants reported in individuals with AI and entered in the AI LOVD.
| Gene (Refseq refs) | No. of variants | Families no. (%) | Variants identified in ≥3 families; number of families: reported nationality/ethnicity | Mode of inheritance and trends in variants identified |
|---|---|---|---|---|
|
FAM83H NM_198488.3 NP_940890.3 |
26 | 52 (19.3) | c.973C>T, p.(L31R), 3: Korean and Chinese; c.1192C>T, 5: Korean, Turkish, Caucasian, N/R; c.1354C>T, p.(Q452*), 5: Korean, Danish, Chinese, Jewish, Caucasian; c.2029C>T, p.(Q677*), 5: Korean, Caucasian, N/R. | AD. All within final exon. All except c.1669G>T, p.(G557C), are frameshift/nonsense variants predicted to escape NMD. |
|
FAM20A NM_017565.3 NP_060035.2 |
42 | 41 (15.2) | c.34_35delCT, p.(L12Afs*67), 5: Pakistani, Moroccan, Korean/Turkish, N/R; c.406C>T, p.(R136*), 3: Brazilian, Omani, Iranian. | AR. Most are nonsense/frameshift. Three missenses reported: c.518T>G, p.(L173R), c.992T>G, p.(G331D), c.1207G>A, p.(D403N). |
|
ENAM NM_031889.2 NP_114095.2 |
18 | 39 (14.4) | c.92T>G, p.(L31R), 5 families: British; c.157A>T, p.(K53*), 7: Swedish; c.588+1delG, p.?, 5: Japanese, Lebanese, Slovenian, N/R; c.1259_1260insAG, p.(V422Pfs*27), 7: Turkish, Slovenian, N/R. | AD (AR also reported). Most are protein-truncating. In-frame indels and missense variants also identified. |
|
AMELX NM_182680.1 NP_872621.1 |
22 | 31 (11.5) | c.208C>A, p.(P70T), 6: North American, N/R; c.473delC, p.(P158Hfs*31), 3: North American, British. | XLD. Most are protein-truncating variants. Missense variants affect the N-terminus. |
|
DLX3 NM_005220.2 NP_005211.1 |
6 | 15 (5.6) | c.561_562delCT, p.(Y166Qfs*13), 4: Australian, Korean, Caucasian, Turkish; c.571_574delGGGG, p.(G191Rfs*66), 7: North American. | AD. Most are missenses in homeodomain, other two are frameshifts predicted to escape NMD and to affect C-terminal transactivation domain. |
|
MMP20 NM_004771.3 NP_004762.2 |
11 | 13 (4.8) | c.389C>T, p.T130I, 3: French, N/R c.678T>A, p.H226Q, 3: Turkish, North American, N/R. c.954-2A>T, p.?, 4: North American, French/German/Moroccan. | AR. Variety of missense, frameshift, splice and nonsense variants reported. |
|
WDR72 NM_182758.3 NP_877435.3 |
10 | 12 (4.4) | c.1467_1468delAT, p.(V491Dfs*8), 3: Mexican, Turkish, unknown. | AR. All are nonsense/frameshift predicted to under-go NMD, except missense variant c.182A>G, p.(H61R). |
|
COL17A1 NM_000494.3 NP_000485.3 |
10 | 12*∧ (4.4) | N/A | AD. Nonsense/frameshift variants predicted to undergo NMD, and missense variants affecting glycine residues. |
|
C4orf26 NM_178497.3 NP_848592.2 |
6 | 10* (3.7) | c.51_56delGGTAACinsATGCTGGTTACTGGTA, p.(V18Cfs*23), 3: North American; c.229C>T, p.(R77*), 4: Omani. | AR. All nonsense/frameshift/splice variants. Nonsense/frameshifts predicted to escape NMD. |
|
LAMB3 NM_000228.2 NP_000219.2 |
9 | 9 (3.3) | N/A | AD. Majority frameshift/nonsense. Most lead to stop codon in penultimate/final exon. Two variants within other exons identified. |
|
KLK4 NM_004917.4 NP_004908.4 |
4 | 9 (3.3) | c.632delT, p.(L211Rfs*37), 5: Pakistani. | AR. All are nonsense/frameshift. Not all are predicted to undergo NMD. |
|
ACPT NM_033068.2 NP_149059.1 |
7 | 8 (3.0) | c.713C>T, p.(S238L), 3: Turkish. | AR. All missense variants within the extracellular domain. |
|
SLC24A4 NM_153646.3 NP_705932.2 |
5 | 6 (2.2) | N/A | AR. Variety reported, including a multi-exon deletion, a nonsense and missense variants. |
|
ITGB6 NM_000888.4 NP_000879.2 |
6 | 5 (1.9) | N/A | AR. All missense variants except one nonsense variant, c.1846C>T, p.(R616*). |
|
LAMA3 NM_000227.3 NP_00218.2 |
4 | 4∧ (1.5) | N/A | AD. All frameshift, nonsense or splice variants. |
|
GPR68 NM_001177676.1 NP_001171147.1 |
3 | 3 (1.1) | N/A | AR. One frameshift, one in-frame deletion, one missense variant. |
|
AMBN NM_016519.5 NP_057603.1 |
2 | 2 (0.7) | N/A | AR. One in-frame exon deletion, one splice variant. |
|
AMTN NM_212557.3 NP_997722.1 |
1 | 1 (0.4) | N/A | AD. One variant: a multi-exon, in-frame deletion. |
| Total | 192 | 270∧ |
Genes are ordered in decreasing number of families reported. No. of variants denotes the number of unique variants reported for each gene within the AI LOVD. Nationality/ethnicity is as reported, in some cases, multiple families are reported within one study with only details of the nationalities/ethnicities of the cohort included but with no specific nationality/ethnicity assigned to each individual/family. In such cases, all nationalities/ethnicities have been listed. The inheritance of disease due to ENAM variants has been reported to be AR in some instances, however heterozygous and biallelic individuals for ENAM variants were reported to have a milder and more severe phenotype, respectively.
one family carries variants in both COL17A1 and C4orf26.
one family carries variants in both COL17A1 and LAMA3. Therefore, total number of families is 270 not 272. AD, autosomal dominant; AR, autosomal recessive; NMD, nonsense mediated decay; N/A, not applicable; N/R, not reported; XLD, X-linked dominant. Data obtained from AI LOVD: http://dna2.leeds.ac.uk/LOVD/ 23rd May 2017.