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Abstract：
Tumor protein p63 (TP63)-related disorders can be divided into at least six categories, including ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome 3 (EEC syndrome 3), ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC syndrome), acro-dermo-ungual-lacrimal-tooth syndrome (ADULT syndrome), limb-mammary syndrome (LMS), Rapp-Hodgkin syndrome (RHS) and split-hand/foot malformation 4 (SHFM4), and are all a result of heterozygous mutations of TP63. The phenotypes of TP63-related disorders broadly involve ectodermal dysplasias, acromelic malformation and orofacial cleft. SHFM and hypodontia are prominent clinical manifestations of TP63-related disorders.
The present study investigated a family with SHFM and hypodontia; determined the sequences of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1 and FGFR1; and performed single nucleotide polymorphism-array analysis. We detected the mutation by multiple sequence alignments and a bioinformatic prediction.
We identified a novel missense mutation of TP63 (c.1010G>T; R337L) in the family without mutations of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1, FGFR1 and copy number variants causing SHFM.
A mutation of TP63 (c.1010G>T; R337L) leads to SHFM with hypodontia. The identification of this mutation expands the spectrum of known TP63 mutations and also may contribute to novel approaches for the genetic diagnosis and counseling of families with TP63-related disorders.
The present study investigated a family with SHFM and hypodontia; determined the sequences of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1 and FGFR1; and performed single nucleotide polymorphism-array analysis. We detected the mutation by multiple sequence alignments and a bioinformatic prediction.
We identified a novel missense mutation of TP63 (c.1010G>T; R337L) in the family without mutations of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1, FGFR1 and copy number variants causing SHFM.
A mutation of TP63 (c.1010G>T; R337L) leads to SHFM with hypodontia. The identification of this mutation expands the spectrum of known TP63 mutations and also may contribute to novel approaches for the genetic diagnosis and counseling of families with TP63-related disorders.
摘要：
肿瘤蛋白p63（TP63）相关疾病可分为至少六类，包括外趾-外胚层发育不良-唇腭裂综合征3（EEC综合征3），唇-外胚层缺损-唇腭裂综合征（AEC综合征），肩-皮-甲-泪牙综合征（ADULT综合征），肢体乳腺综合征（LMS），拉普-霍奇金综合征（RHS）和手/足分裂畸形4（SHFM4），都是TP63杂合突变的结果。TP63相关疾病的表型广泛涉及外胚层发育不良，肢端畸形和口面裂。SHFM和牙髓不足是TP63相关疾病的突出临床表现。
本研究调查了一个具有SHFM和低体的家族;确定了DLX5，WNT8B，WNT10B,BHLHA9，CDH3，DYNC1I1和FGFR1；并进行了单核苷酸多态性阵列分析。我们通过多个序列比对和生物信息学预测检测到突变。
我们在没有DLX5，WNT8B突变的家族中鉴定了TP63（c.1010G>T;R337L）的新错义突变，WNT10B,BHLHA9、CDH3、DYNC1I1、FGFR1和拷贝数变异导致SHFM。
TP63的突变(c.1010G>T;R337L)导致具有低体的SHFM。这种突变的鉴定扩展了已知的TP63突变的范围，也可能有助于对患有TP63相关疾病的家庭进行遗传诊断和咨询的新方法。
本研究调查了一个具有SHFM和低体的家族;确定了DLX5，WNT8B，WNT10B,BHLHA9，CDH3，DYNC1I1和FGFR1；并进行了单核苷酸多态性阵列分析。我们通过多个序列比对和生物信息学预测检测到突变。
我们在没有DLX5，WNT8B突变的家族中鉴定了TP63（c.1010G>T;R337L）的新错义突变，WNT10B,BHLHA9、CDH3、DYNC1I1、FGFR1和拷贝数变异导致SHFM。
TP63的突变(c.1010G>T;R337L)导致具有低体的SHFM。这种突变的鉴定扩展了已知的TP63突变的范围，也可能有助于对患有TP63相关疾病的家庭进行遗传诊断和咨询的新方法。
