Triangular tibia with fibular aplasia associated with a microdeletion on 2q11.2 encompassing LAF4
Triangular tibia with fibular aplasia associated with a microdeletion on 2q11.2 encompassing LAF4
复制标题
三角胫骨伴有腓骨发育不全，与包含 LAF4 的 2q11.2 上的微缺失有关
作者：
E. Steichen‐Gersdorf;I. Gassner;A. Superti;R. Ullmann;S. Stricker;E. Klopocki;S. Mundlos
Nievergelt综合征（NS）是一种常染色体显性遗传的中肢发育不良，其特征是桡骨、尺骨、腓骨和胫骨菱形的特异性畸形。表型重叠的条件，如中肢发育不良，Savarirayan型（MIM 605274），已被描述，但其发病机制也仍然未知。我们报告一个女孩腓骨发育不全，严重异常，三角胫骨，泌尿生殖道畸形，未能茁壮成长，惊厥和反复呼吸暂停导致呼吸停止，在4个月的年龄。 她的骨骼检查结果与最近在两名患者中描述的Savarirayan型中肢发育不良相对应。除了骨骼的发现，我们的病人有中枢神经系统的表现和发育异常的泌尿生殖道。在本研究描述的患者中，阵列比较基因组杂交（CGH）分析显示，染色体2q11.1上存在500 kb的从头间质微缺失，包含LAF 4/AFF 3（淋巴核蛋白相关AF 4）基因。 Laf 4在小鼠胚胎中的原位杂交分析显示，在发育中的大脑，在肢芽和在对应于肢体表型的zeugopod中的表达。LAF 4/AFF 3的单倍不足与肢体、脑和泌尿生殖系统畸形以及作为NS谱的一部分的胫骨的特定变化相关。
Nievergelt syndrome (NS) is an autosomal dominant mesomelic dysplasia characterized by specific deformities of the radius, ulna, fibula and a rhomboid shape of the tibia. Phenotypically overlapping conditions such as mesomelic dysplasia, Savarirayan‐type (MIM 605274), have been described, but their pathogenesis also remains unknown. We report on a girl with fibular agenesis, severely abnormal, triangular tibiae, urogenital tract malformations, failure to thrive, convulsions and recurrent apnoeas leading to respiratory arrest at the age of 4 months. Her skeletal findings correspond to those of the mesomelic dysplasia, Savarirayan‐type recently described in two patients. In addition to the skeletal findings, our patient had central nervous system manifestations and developmental anomalies of the urogenital tract. In the patient described in this study, array comparative genomic hybridization (CGH) analysis revealed a de novo interstitial microdeletion of 500 kb on chromosome 2q11.1 containing the LAF4/AFF3 (lymphoid‐nuclear‐protein‐related AF4) gene. In situ hybridization analysis of Laf4 in mouse embryos revealed expression in the developing brain, in the limb buds and in the zeugopod corresponding to the limb phenotype. Haploinsufficiency for LAF4/AFF3 is associated with limb, brain and urogenital malformations and specific changes of the tibia that are part of the NS spectrum.
中粒发育不良伴腓骨缺失和六指畸形：尼弗格尔特综合征还是新综合征？
DOI：
10.1002/ajmg.1320370104
发表时间：
1990
期刊：
American journal of medical genetics
影响因子：
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作者：
Petrella,R;Ludman,MD;Rabinowitz,JG;Gilbert,F;Hirschhorn,K
通讯作者：
Hirschhorn,K