Abstract：
Critical genes involved in embryonic development are often transcription factors, regulating many downstream genes. LMX1B is a homeobox gene that is involved in formation of the limbs, eyes and kidneys, heterozygous loss-of-function sequence variants and deletions cause Nail-Patella syndrome. Most of the reported variants are localised within the gene\'s coding sequence, however, approximately 5%-10% of affected individuals do not have a pathogenic variant identified within this region. In this study, we present a family with four affected individuals across two generations with a deletion spanning a conserved upstream LMX1B-binding sequence. This deletion is de novo in the mother of three affected children. Furthermore, in this family, the manifestations appear limited to the nails and limbs, and therefore may reflect an attenuated phenotype of the classic Nail-Patella phenotype that includes ophthalmological and renal manifestations.
摘要：
参与胚胎发育的关键基因通常是转录因子，调节许多下游基因。LMX1B是一种参与四肢形成的同源盒基因，眼睛和肾脏，杂合功能缺失序列变异和缺失导致甲髌骨综合征。大多数报道的变异都位于基因的编码序列内，然而,大约5％-10％的受影响的个体没有在该区域内确定的致病变异。在这项研究中,我们提供了一个家族,该家族在两代中有4个受影响的个体,其缺失跨越保守的上游LMX1B结合序列.该删除在三个受影响儿童的母亲中是从头删除的。此外，在这个家庭里,这些表现似乎仅限于指甲和四肢，因此，可能反映了经典指甲髌骨表型的减弱表型，包括眼科和肾脏表现。
