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首页> 外文期刊>BMC Medical Genetics >Bilateral radial agenesis with absent thumbs, complex heart defect, short stature, and facial dysmorphism in a patient with pure distal microduplication of 5q35.2-5q35.3
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Bilateral radial agenesis with absent thumbs, complex heart defect, short stature, and facial dysmorphism in a patient with pure distal microduplication of 5q35.2-5q35.3

机译：单纯远端显微重复为5q35.2-5q35.3的患者出现双侧s骨发育不全，拇指缺失，心脏复杂缺陷，身材矮小和面部畸形

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Background A partial duplication of the distal long arm of chromosome 5 (5q35--?>?qter) is known to be associated with a distinct phenotype referred to as Hunter-McAlpine syndrome. Clinical spectrum of this disorder mainly consists of mental retardation, microcephaly, short stature, skeletal anomalies, and craniofacial dysmorphism featuring flat facies, micrognathia, large, low-set dysplastic ears, hypertelorism, almond-shaped, down-slanted palpebral fissures, epicanthal folds, small nose, long philtrum, small mouth, and thin upper lip. Less frequent remarkable findings include craniosynostosis, heart defect, hypoplastic phalanges, preaxial polydactyly, hypospadias, cryptorchidism, and inguinal hernia. In most patients with a partial duplication of 5q the aberration occurred due to an inherited unbalanced translocation, therefore the phenotype was not reflective of pure trisomy 5q. Case presentation We report on a 9.5-year-old boy with some feature of Hunter-McAlpine syndrome including short stature, complex heart defect (dextrocardia, dextroversion, PFO), bilateral cryptorchidism, hypothyroidism, and craniofacial dysmorphism. Additionally, bilateral radial agenesis with complete absence of Ist digital rays, ulnar hypoplasia with bowing, choroidal and retinal coloboma, abnormal biliary vesicle were identified, which have never been noted in 5q trisomy patients. Karyotype analysis, sequencing and MLPA for TBX5 and SALL4 genes were unremarkable. Array comparative genomic hybridization detected a duplication on 5q35.2-5q35.3, resulting from a de novo chromosomal rearrangement. Our proband carried the smallest of all previously reported pure distal 5q trisomies encompassing terminal 5.4-5.6 Mb and presented with the most severe limb malformation attributed to the increased number of distal 5q copies. Conclusions We postulate that a terminal distal trisomy of 5q35.2-5q35.3, which maps 1.1 Mb telomeric to the MSX2 gene is causative for both radial agenesis and complex heart defect in our proband. A potential candidate gene causative for limb malformation in our proband could be FGFR4 , which maps relatively in the closest position to the chromosomal breakage site (about 1.3 Mb) from all known 5q duplications. Since the limb malformation as well as the underlying genetic defect are distinct from other 5q trisomy patient we propose that a position effect resulting in altered long-range regulation of the FGFR4 (alternatively MSX2 ) may be responsible for the limb malformation in our proband.
机译：背景已知5号染色体的远端长臂的部分重复（5q35--Δqter）与一种独特的表型有关，被称为Hunter-McAlpine综合征。该疾病的临床表现主要包括智力低下，小头畸形，身材矮小，骨骼异常和颅面畸形，特征是面相扁平，微棘突，大，低位发育异常的耳朵，过度肌肉发达，杏仁形，向下倾斜的睑裂，上褶，小鼻子，长发t，小嘴巴和薄薄的上唇。较少见的显着发现包括颅突狭窄，心脏缺陷，发育不全指骨，前轴多指，尿道下裂，隐睾症和腹股沟疝。在大多数5q部分重复的患者中，由于遗传的不平衡易位而发生了像差，因此该表型不能反映5q三体性。病例报告我们报告了一个9.5岁男孩，患有一些Hunter-McAlpine综合征特征，包括身材矮小，复杂的心脏缺陷（右旋心，右旋，PFO），双侧隐睾，甲状腺功能减退和颅面畸形。此外，还发现了完全不存在Ist数字射线的双侧radial骨发育不全，伴有弓法的尺骨发育不全，脉络膜和视网膜结肠炎，胆囊异常，这些在5q三体性患者中从未发现过。 TBX5和SALL4基因的核型分析，测序和MLPA均不显着。阵列比较基因组杂交检测到5q35.2-5q35.3重复，这是由于从头染色体重排所致。我们的先证者携带的所有先前报道的纯净远端5q三体症中最小，涵盖末端5.4-5.6 Mb，并且由于远端5q拷贝数的增加，肢体畸形最严重。结论我们推测，在我们的先证者中，末端远侧三体性5q35.2-5q35.3（将1.1 Mb端粒映射到MSX2基因）对radial骨发育不全和复杂的心脏缺陷均是致病原因。在我们的先证者中，可能导致肢体畸形的潜在候选基因可能是FGFR4，它相对于所有已知的5q重复基因都位于最接近染色体断裂位点（约1.3 Mb）的位置。由于肢体畸形以及潜在的遗传缺陷与其他5q三体症患者不同，因此我们建议，导致FGFR4远程调节改变的位置效应（或者MSX2）可能是我们先证者肢体畸形的原因。

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