Expanding the genetic and phenotypic spectrum of popliteal pterygium disorders.
Expanding the genetic and phenotypic spectrum of popliteal pterygium disorders.
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DOI：
10.1002/ajmg.a.36896
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发表时间：
2015-03
影响因子：
2
通讯作者：
Dixon, Michael J.
中科院分区：
文献类型：
--
作者：
Leslie, Elizabeth J.;O'Sullivan, James;Cunningham, Michael L.;Singh, Ankur;Goudy, Steven L.;Ababneh, Faroug;Alsubaie, Lamia;Ch'ng, Gaik-Siew;van der Laar, Ingrid M. B. H.;Hoogeboom, A. Jeannette M.;Dunnwald, Martine;Kapoor, Seema;Jiramongkolchai, Pawina;Standley, Jennifer;Manak, J. Robert;Murray, Jeffrey C.;Dixon, Michael J.
肘部翼状胬肉综合征是数百种孟德尔口面部裂症候群的一个独特的子集。延性翼状胬肉综合征在严重程度和相关表型特征上有相当大的差异，但都以一个或多个主要关节上的皮肤网状物、唇裂和/或腭裂、并指和生殖器畸形为特征。IRF6基因杂合突变可导致延髓翼状胬肉综合征(PPS)，而RIPK4或Chuk(Ikka)纯合子突变分别导致更严重的Bartsoas-Papas综合征(BPS)和蚕茧综合征。在这项研究中，我们报告了6个患有PPS或BPS儿童的家系突变。应用Sanger和外显子组测序相结合的方法，我们报道了第一例由IRF6纯合子突变引起的常染色体隐性遗传性犁性翼状胬肉综合征，以及第一例由21号染色体单亲二体导致的隐性疾病。我们还证明，RIPK4的突变可以导致PPS-BPS谱上的一系列严重特征，而Ikka的突变可以引起BPS-蚕茧谱上的一系列特征。我们的发现对翼状胬肉综合征家族的遗传咨询具有临床意义，并进一步涉及IRF6、RIPK4和Chuk(Ikka)在控制表皮和颅面发育的潜在相互关联的途径中。
The popliteal pterygia syndromes are a distinct subset of the hundreds of Mendelian orofacial clefting syndromes. Popliteal pterygia syndromes have considerable variability in severity and in the associated phenotypic features but are all characterized by cutaneous webbing across one or more major joints, cleft lip and/or palate, syndactyly, and genital malformations. Heterozygous mutations in IRF6 cause popliteal pterygium syndrome (PPS) while homozygous mutations in RIPK4 or CHUK (IKKA) cause the more severe Bartsocas-Papas syndrome (BPS) and Cocoon syndrome, respectively. In this study we report mutations in six pedigrees with children affected with PPS or BPS. Using a combination of Sanger and exome sequencing, we report the first case of an autosomal recessive popliteal pterygium syndrome caused by homozygous mutation of IRF6 and the first case of uniparental disomy of chromosome 21 leading to a recessive disorder. We also demonstrate that mutations in RIPK4 can cause features with a range of severity along the PPS-BPS spectrum and that mutations in IKKA can cause a range of features along the BPS-Cocoon spectrum. Our findings have clinical implications for genetic counseling of families with pterygia syndromes and further implicate IRF6, RIPK4, and CHUK (IKKA) in potentially interconnected pathways governing epidermal and craniofacial development.
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