Milunsky J M, Zhao G, Maher T A, Colby R, Everman D B
Center for Human Genetics, Boston University School of Medicine, Boston, MA, USA.
Clin Genet. 2006 Apr;69(4):349-54. doi: 10.1111/j.1399-0004.2006.00597.x.
Lacrimo-auriculo-dento-digital syndrome [LADD (MIM 149730)] is an autosomal-dominant multiple congenital anomaly disorder characterized by aplasia, atresia or hypoplasia of the lacrimal and salivary systems, cup-shaped ears, hearing loss, and dental and digital anomalies. Loss of function mutations in FGF10 were recently described in aplasia of the lacrimal and salivary glands [ALSG (MIM 180920; MIM 103420)] (Entesarian et al., Nat Genet 2005: 37: 125-127, Milunsky et al., American College of Medical Genetics Annual Meeting, Dallas, TX, 2005: A100). Due to the significant phenotypic overlap between LADD syndrome and ALSG and the variable expressivity of both the disorders, we hypothesized that FGF10 mutations could also result in LADD syndrome. A de novo missense mutation was found in exon 3 of FGF10 in a 3-year-old female (Family 1) with LADD syndrome. This missense mutation, resulting in a non-conservative amino acid change, was confirmed by restriction enzyme digestion and was not found in 500 control chromosomes. A nonsense mutation was also found in exon 2 of FGF10 (Family 2) in a 19-year-old mother with ALSG and her 2-year-old daughter with LADD syndrome. Previous studies of FGF10 mutant mice have demonstrated abnormalities consistent with ALSG and LADD syndrome. We conclude that ALSG and LADD syndrome may represent variable presentations of the same clinical spectrum caused by FGF10 mutations.
泪腺-耳-齿-指综合征[LADD（MIM 149730）]是一种常染色体显性遗传的多发性先天性异常疾病，其特征为泪腺和唾液腺发育不全、闭锁或发育不良、杯状耳、听力丧失以及牙齿和手指异常。最近在泪腺和唾液腺发育不全[ALSG（MIM 180920；MIM 103420）]中发现了FGF10功能丧失突变（恩泰萨里安等人，《自然遗传学》2005年：37：125 - 127；米伦斯基等人，美国医学遗传学学会年会，得克萨斯州达拉斯，2005年：A100）。由于LADD综合征与ALSG之间存在显著的表型重叠以及这两种疾病的可变表达性，我们推测FGF10突变也可能导致LADD综合征。在一名患有LADD综合征的3岁女性（家系1）中，在FGF10的外显子3中发现了一个新生错义突变。这个错义突变导致了非保守氨基酸变化，经限制性内切酶消化得以证实，且在500条对照染色体中未发现。在一名患有ALSG的19岁母亲及其患有LADD综合征的2岁女儿（家系2）中，还在FGF10的外显子2中发现了一个无义突变。先前对FGF10突变小鼠的研究已证明存在与ALSG和LADD综合征一致的异常。我们得出结论，ALSG和LADD综合征可能代表由FGF10突变引起的同一临床谱系的不同表现形式。
