Pulmonary acinar hypoplasia (PAH) and lacrimo-auriculo-dento-digital (LADD) syndrome have both been associated with loss-of-function variants in, or deletions of FGF10. Here we report a multi-generational family with seven members manifesting varying features of LADD syndrome, with one individual dying in early infancy of PAH. Whole genome sequencing in one family member identified a 12,158 bp deletion on chromosome 5p12 that removes two of the three exons of FGF10. Allele-specific PCR demonstrated that all affected family members, including the individual with PAH, carried the 12 kb deletion. We conclude the deletion is pathogenic and expands the mutational spectrum of FGF10 variants in LADD syndrome. The common mechanism underlying the variable clinical features of LADD syndrome is defective terminal branching of salivary and lacrimal glands and pulmonary acini, regulated by the TBX4-FGF10-FGFR2 pathway. The variable phenotypic expressivity of FGF10 haploinsufficiency from relatively benign to lethal is likely due to variation at other genetic loci.

肺腺泡发育不全（PAH）和泪-耳-齿-指（LADD）综合征均与功能丧失变异或缺失相关。成纤维细胞生长因子10 。在这里，我们报告了一个多代家庭，有 7 名成员，表现出不同的 LADD 综合征特征，其中一人在婴儿早期死于 PAH。对一名家庭成员的全基因组测序发现，染色体 5p12 上存在 12,158 bp 的缺失，该缺失删除了 5p12 染色体的三个外显子中的两个。成纤维细胞生长因子10 。等位基因特异性 PCR 表明，所有受影响的家庭成员，包括 PAH 患者，都携带 12 kb 缺失。我们得出结论，该缺失是致病性的，并扩大了突变谱成纤维细胞生长因子10 LADD 综合征的变异。 LADD 综合征不同临床特征的共同机制是唾液腺、泪腺和肺腺泡的末端分支缺陷，受 TBX4-FGF10-FGFR2 通路调节。可变的表型表达性成纤维细胞生长因子10从相对良性到致命的单倍体不足可能是由于其他基因位点的变异造成的。