TABLE 1.
Summary of ACAN genetic results including nucleotide change, mutation site, mutation type, and clinical phenotype
| Nucleotide change | Exon/intron | Domain | Clinical phenotype | Reference | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S | Body parts involved | OA/OD | Others | BA | GH deficient | SGA | |||||||||
| He/N | Ha/F | C | V | J | |||||||||||
| Nonsense variants (n = 20, 27%) | |||||||||||||||
| 1 | c.61G>T | E2 | G1 | Y | Advanced | Gkourogianni et al. (2017) | |||||||||
| 2 | c.301C>T | E3 | G1 | NA | Stavber et al. (2020) | ||||||||||
| 3 | c.492C>G | E4 | G1 | Y | Y | Advanced | Gkourogianni et al. (2017) | ||||||||
| 4 | c.515del | E4 | G1 | Y | Y | Y | Delay | Hauer et al. (2017) | |||||||
| 5 | c.532A>T | E4 | G1 | Y | Advanced | Y | Gkourogianni et al. (2017) | ||||||||
| 6 | c.1047_1048dellinsAC | E6 | G1 | Y | Y | NA | Gkourogianni et al. (2017) | ||||||||
| 7 | c.1180C>T | E7 | IGD | Y | Y | Y | Y | Delay | Hauer et al. (2017) | ||||||
| 8 | c.1411C>T | E7 | IGD | Y | Y | Y | Advanced | Liang et al. (2020) | |||||||
| 9 | c.1443G>T | E7 | IGD | Y | Y | Y | NA | Gkourogianni et al. (2017) | |||||||
| 10 | c.1526C>A | E8 | G2 | Y | NA | Gkourogianni et al. (2017) | |||||||||
| 11 | c.1608C>A | E9 | G2 | Y | Y | Y | Absent left kidney | Normal/advanced | Y | van der Steen et al. (2017) | |||||
| 12 | c.1762C>T | E10 | G2 | Y | Y | Delay | Liang et al. (2020) | ||||||||
| 13 | c.1774C>T | E10 | G2 | Y | Y | Normal | Hauer et al. (2017) | ||||||||
| 14 | c.2099G>A | E11 | KS | Y | NA | Stavber et al. (2020) | |||||||||
| 15 | c.2369C>G | E12 | KS | Y | Advanced | Y | Sentchordi‐Montané et al. (2018) | ||||||||
| 16 | c.4657G>T | E12 | CS | Y | Y | Y | NA | Gkourogianni et al. (2017) | |||||||
| 17 | c.4852C>T | E12 | CS | Y | Y | Delay | Y | Tatsi et al. (2017) | |||||||
| 18 | c.5597C>A | E12 | CS | Y | Y | Y | Advanced | Hauer et al. (2017) | |||||||
| 19 | c.7090C>T | E12 | G3 | Y | Y | Y | Y | Advanced | Y | van der Steen et al. (2017) | |||||
| 20 | c.7203G>A | E16 | G3 | Y | Y | NA | Gkourogianni et al. (2017) | ||||||||
| Missense variants (n = 30, 40.5%) | |||||||||||||||
| 1 | c.151T>G | E3 | G1 | Y | Y | Advanced | Y | Hauer et al. (2017) | |||||||
| 2 | c.223T>C | E3 | G1 | Y | Y | Advanced | Gkourogianni et al. (2017) | ||||||||
| 3 | c.371G>A | E3 | G1 | Delay | Sentchordi‐Montané et al. (2018) | ||||||||||
| 4 | c.742G>A | E5 | G1 | Y | Y | Normal | Gkourogianni et al. (2017) | ||||||||
| 5 | c.903G>C | E6 | G1 | Y | Y | Y | Y | Normal | Gkourogianni et al. (2017) | ||||||
| 6 | c.916A>T | E6 | G1 | Y | Advanced | Gkourogianni et al. (2017) | |||||||||
| 7 | c.1046A>G | E6 | G1 | Y | NA | Hattori et al. (2017) | |||||||||
| 8 | c.1598C>T | E9 | G2 | Y | Normal | Sentchordi‐Montané et al. (2018) | |||||||||
| 9 | c.1702G>A | E9 | G2 | Y | Y | Y | Delay | Hauer et al. (2017) | |||||||
| 10 | c.1817C>A | E10 | G2 | Y | Y | Y | Café‐au‐lait Spots | Delay | Liang et al. (2020) | ||||||
| 11 | c.1930G>A | E10 | G2 | Y | Normal | Sentchordi‐Montané et al. (2018) | |||||||||
| 12 | c.1948G>A | E10 | G2 | Y | Delay | Sentchordi‐Montané et al. (2018) | |||||||||
| 13 | c.1979C>T | E10 | G2 | Y | NA | Hattori et al. (2017) | |||||||||
| 14 | C.2164C>G | E11 | KS | Precocious puberty | Advanced | Wang et al. (2020) | |||||||||
| 15 | c.2218A>T | E11 | KS | Y | Normal | Sentchordi‐Montané et al. (2018) | |||||||||
| 16 | c.2266G>C | E11 | KS | Y | Y | Y | Advanced | Liang et al. (2020) | |||||||
| 17 | c.4138G>T | E12 | CS | Y | Y | Y | Hypertension | NA | Fukuhara et al. (2019) | ||||||
| 18 | c.5061T>A | E12 | CS | Y | Y | Y | Hypertension | NA | Fukuhara et al. (2019) | ||||||
| 19 | c.6142C>G | E12 | CS | Y | Normal | Y | Sentchordi‐Montané et al. (2018) | ||||||||
| 20 | c.6799G>A | NA | G3 | Y | Y | Y | Y | Y | NA | Tompson et al. (2009) | |||||
| 21 | c.6907G>A | NA | G3 | Y | NA | Stattin et al. (2010) | |||||||||
| 22 | c.6970T>C | NA | G3 | Y | Y | Y | Delay | Florio et al. (2019) | |||||||
| 23 | c.7064T>C | E12 | G3 | Y | Y | Y | Y | Normal | Nilsson et al. (2014) | ||||||
| 24 | c.7069A>T, | E12 | G3 | Y | NA | Stavber et al. (2020) | |||||||||
| 25 | c.7153G>A | E15 | G3 | Y | Y | NA | Gkourogianni et al. (2017) | ||||||||
| 26 | c.7276G>T | E16 | G3 | Y | Advanced | Y | Gkourogianni et al. (2017) | ||||||||
| 27 | c.7276G>A | E16 | G3 | Y | Normal | Y | Sentchordi‐Montané et al. (2018) | ||||||||
| 28 | c.7429G>A | E16 | G3 | Y | NA | Gkourogianni et al. (2017) | |||||||||
| 29 | c.7465T>C | NA | G3 | Y | Delay | Xu et al. (2018) | |||||||||
| 30 | c.7469G>A | E18 | G3 | Y | Y | Y | Delay | Liang et al. (2020) | |||||||
| Frameshift variants (n = 18, 24.3%) | |||||||||||||||
| 1 | c.6_13delCACTTTAC | E2 | G1 | Y | Delay | Y | Hu et al. (2017) | ||||||||
| 2 | c.116dupT | E3 | G1 | Y | Y | Y | Delay | This article | |||||||
| 3 | c.272delA | E3 | G1 | Diabetes | Advanced | Y | Nilsson et al. (2014) | ||||||||
| 4 | c.410_418delinsTGGA | E3 | G1 | NA | Stavber et al. (2020) | ||||||||||
| 5 | c.661delT | E5 | G1 | Acanthosis nigricans | Normal | Y | Hu et al. (2017) | ||||||||
| 6 | c.1117_1120delCAGA | E7 | IGD | Y | Normal | Y | Hu et al. (2017) | ||||||||
| 7 | c.1425delA | E8 | G2 | Y | NA | Gkourogianni et al. (2017) | |||||||||
| 8 | c.1733‐1G>A | I9 | G2 | Y | Normal | Liang et al. (2020) | |||||||||
| 9 | c.1744delT | E10 | G2 | Y | Y | Y | Advanced | Y | Dateki et al. (2017) | ||||||
| 10 | c.2367delC | E12 | KS | Y | Pre cocious puberty | Advanced | This article | ||||||||
| 11 | c.2535_2536 insTTCA | E12 | KS | Y | NA | Hattori et al. (2017) | |||||||||
| 12 | c.4762_4765del | E12 | CS | Y | Advanced | Y | van der Steen et al. (2017) | ||||||||
| 13 | c.5391delG | E12 | CS | Y | Advanced | Quintos et al. (2015) | |||||||||
| 14 | c.6193delC | E12 | CS | Y | Advanced | ZENG et al. (2018) | |||||||||
| 15 | c.6404delC | E12 | CS | Y | Advanced | Y | Tatsi et al. (2017) | ||||||||
| 16 | c.7041delG | E12 | G3 | Y | NA | Stavber et al. (2020) | |||||||||
| 17 | c.7222dupA | E16 | G3 | Y | Advanced | Yang et al. (2018) | |||||||||
| 18 | c.7269delG | E15 | G3 | Y | Advanced | Sentchordi‐Montané et al. (2018) | |||||||||
| Splicing variants (n = 1, 1.4%) | |||||||||||||||
| 1 | c.2026+1G>A | I10 | G2 | Y | Y | Y | Normal | Nilsson et al. (2014) | |||||||
| Deletions (n = 2, 2.7%) | |||||||||||||||
| 1 | c.71_1051del | E12 | G3 | Y | Y | Y | Y | NA | Stavber et al. (2020) | ||||||
| 2 | c.7093_7095 delGAG | E15 | G3 | Y | NA | Hattori et al. (2017) | |||||||||
| Translocation (n = 1, 1.4%) | |||||||||||||||
| 1 | t (10; 15) (q22.3; q26.1) | I1 | NA | Y | Normal | Crippa et al. (2018) | |||||||||
| Unknown (n = 2, 2.7%) | |||||||||||||||
| 1 | c‐7‐2A>C* | I1 | NA | Y | Delay | Y | Sentchordi‐Montané et al. (2018) | ||||||||
| 2 | c.7342G>A | E17 | G3 | Y | Normal | Sentchordi‐Montané et al. (2018) | |||||||||
Abbreviations: BA, bone age; C, chest abnormity, including pectus excavatum/barrel chests/rib valgus et al; Ha/F, hands/feet abnormity, including short thumbs/short metacarpal bones/broad great toes/flat feet et al; He/N, head/neck abnormity, including macrocephaly/midface hypoplasia/prominent forehead/broad forehead/flat nasal bridge/low‐set ears/posteriorly rotated ears/short neck et al; J, joint abnormity, including cubitus valgus/internal rotation of elbow/patellar (sub) luxation et al; NA, not available; OA/OD, osteoarthritis/osteochondritis; S, short only; SGA, small for gestational age; V, vertebral abnormity, including lumbar lordosis/scoliosis/spine deformity/lumbar disk herniation et al.