Amelogenesis imperfecta type IG (AI1G) is caused by mutations in FAM20A. Genotypic and phenotypic features of AI1G are diverse and their full spectra remain to be characterized. The aim of this study was to identify and summarize variants in FAM20A in a broad population of patients with AI1G. We identified a Thai female (Pt-1) and a Saudi male (Pt-2) affected with AI1G. Both had hypoplastic enamel, gingival hyperplasia, and intrapulpal calcification. Pt-1 also had rapidly progressive embedding of unerupted teeth, early eruption of permanent teeth, and spontaneous dental infection. Uniquely, Pt-2 had all permanent teeth erupted which was uncommon in AI1G patients. Whole exome sequencing (WES) identified that Pt-1 was heterozygous for FAM20A, c.758A > G (p.Tyr253Cys), inherited from her father. The mutation on maternal allele was not detected by WES. Pt-2 possessed compound heterozygous mutations, c.1248dupG (p.Phe417Valfs*7); c.1081C > T (p.Arg361Cys) in FAM20A. Array comparative genomic hybridization (aCGH), cDNA sequencing, and whole genome sequencing successfully identified 7531 bp deletion on Pt-1’s maternal allele. This was the largest FAM20A deletion ever found. A review of all 70 patients from 50 independent families with AI1G (including two families in this study) showed that the penetrance of hypoplastic enamel and gingival hyperplasia was complete. Unerupted permanent teeth were found in all 70 patients except Pt-2. Exons 1 and 11 were mutation-prone. Most mutations were frameshift. Certain variants showed founder effect. To conclude, this study reviews and expands phenotypic and genotypic spectra of AI1G. A large deletion missed by WES can be detected by WGS. Hypoplastic enamel, gingival hyperplasia, and unerupted permanent teeth prompt genetic testing of FAM20A. Screening of nephrocalcinosis, early removal of embedded teeth, and monitoring of dental infection are recommended.

IG的促成胎不全症（AI1G）是由FAM20A中的突变引起的。AI1G的基因型和表型特征是多种多样的，其完整光谱仍有待表征。这项研究的目的是在广泛的AI1G患者群体中鉴定和总结FAM20A的变异体。我们确定了感染AI1G的泰国女性（Pt-1）和沙特男性（Pt-2）。两者都有发育不良的牙釉质，牙龈增生和肺内钙化。Pt-1还具有快速进行性的埋没未张开的牙齿，早期萌出恒牙和自发性牙齿感染的能力。独特的是，Pt-2的所有恒牙均脱落，这在AI1G患者中并不常见。全外显子组测序（WES）鉴定出Pt-1对FAM20A是杂合的，c.758A> G（p.Tyr253Cys），继承自她父亲。WES未检测到母体等位基因上的突变。的Pt-2具有化合物杂合突变， c.1248dupG（p.Phe417Valfs * 7）; FAM20A中的c.1081C> T（p.Arg361Cys）。阵列比较基因组杂交（aCGH），cDNA测序和全基因组测序成功鉴定出Pt-1的母亲等位基因上的7531 bp缺失。这是最大的FAM20A发现删除。对来自50个独立家庭的AI1G（包括本研究中的两个家庭）的所有70例患者进行的检查显示，增生性釉质和牙龈增生的穿透性是完全的。除Pt-2外，在所有70例患者中均发现了未破裂的恒牙。外显子1和11易发生突变。大多数突变是移码。某些变体显示了创始人效应。总而言之，这项研究回顾并扩展了AI1G的表型和基因型谱。WGS可以检测到WES遗漏的大量删除。发育不良的牙釉质，牙龈增生和未脱落的恒牙促使FAM20A的基因检测。建议筛查肾钙质沉着症，及早清除嵌入的牙齿并监测牙齿感染。