Abstract：
UNASSIGNED: Ectrodactyly is a rare congenital limb malformation characterized by a deep median cleft of the hand and/or foot due to the absence of central rays. It could be isolated or depicts a part of diverse syndromic forms. Heterozygous pathogenic variants in the TP63 gene are responsible for at least four rare syndromic human disorders associated with ectrodactyly. Among them, ADULT (Acro-Dermato-Ungual-Lacrimal-Tooth) syndrome is characterized by ectodermal dysplasia, excessive freckling, nail dysplasia, and lacrimal duct obstruction, in addition to ectrodactyly and/or syndactyly. Ophthalmic findings are very common in TP63-related disorders, consisting mainly of lacrimal duct hypoplasia. Absent meibomian glands have also been well documented in EEC3 (Ectrodactyly Ectodermal dysplasia Cleft lip/palate) syndrome but not in ADULT syndrome.
UNASSIGNED: We report a case of syndromic ectrodactyly consistent with ADULT syndrome, with an additional ophthalmic manifestation of agenesis of meibomian glands. The proband, as well as her elder sister, presented with congenital cone dystrophy.The molecular investigation was performed in the proband using Whole Exome Sequencing. Family segregation of the identified variants was confirmed by Sanger sequencing.
UNASSIGNED: Two clinically relevant variants were found in the proband: the novel de novo heterozygous missense c.931A > G (p.Ser311Gly) in the TP63 gene classified as pathogenic, and the homozygous nonsense pathogenic c.1810C > T (p.Arg604Ter) in the CNGB3 gene. The same homozygous CNGB3 variation was also found in the sister, explaining the cone dystrophy in both cases.
UNASSIGNED: Whole Exome Sequencing allowed dual molecular diagnoses: de novo TP63-related syndromic ectrodactyly and familial CNGB3-related congenital cone dystrophy.
UNASSIGNED: We report a case of syndromic ectrodactyly consistent with ADULT syndrome, with an additional ophthalmic manifestation of agenesis of meibomian glands. The proband, as well as her elder sister, presented with congenital cone dystrophy.The molecular investigation was performed in the proband using Whole Exome Sequencing. Family segregation of the identified variants was confirmed by Sanger sequencing.
UNASSIGNED: Two clinically relevant variants were found in the proband: the novel de novo heterozygous missense c.931A > G (p.Ser311Gly) in the TP63 gene classified as pathogenic, and the homozygous nonsense pathogenic c.1810C > T (p.Arg604Ter) in the CNGB3 gene. The same homozygous CNGB3 variation was also found in the sister, explaining the cone dystrophy in both cases.
UNASSIGNED: Whole Exome Sequencing allowed dual molecular diagnoses: de novo TP63-related syndromic ectrodactyly and familial CNGB3-related congenital cone dystrophy.
摘要：
■Ectrodactyly是一种罕见的先天性肢体畸形，其特征是由于没有中央射线而导致手和/或脚的深正中裂。它可以是孤立的或描绘不同的综合征形式的一部分。TP63基因中的杂合致病变体负责至少四种与异位相关的罕见综合征人类疾病。其中,成人（Acro-Dermato-Ungual-Local-Tooth）综合征的特征是外胚层发育不良，过多的雀斑,指甲发育不良,和泪管阻塞,除了代指和/或代指。眼科发现在TP63相关疾病中非常常见，主要由泪道发育不全构成。EEC3（外胚层发育不良唇腭裂）综合征也有很好的记录，但在成人综合征中没有。
■我们报告了一例与成人综合征一致的综合征性异位，具有睑板腺发育不全的额外眼科表现。先证者，和她的姐姐一样，表现为先天性视锥细胞营养不良。使用全外显子组测序在先证中进行分子研究。通过Sanger测序确认鉴定的变体的家族分离。
■在先证中发现了两个临床相关的变体：新的从头杂合错义c.931A>G（p。Ser311Gly）在TP63基因中被归类为致病性，纯合无义致病性c.181C>T（p。Arg604Ter）在CNGB3基因中。在姐妹中也发现了相同的纯合CNGB3变异，解释这两种情况下的锥体营养不良。
■整个外显子组测序允许双重分子诊断：从头TP63相关的综合征性异位和家族性CNGB3相关的先天性视锥细胞营养不良。
■我们报告了一例与成人综合征一致的综合征性异位，具有睑板腺发育不全的额外眼科表现。先证者，和她的姐姐一样，表现为先天性视锥细胞营养不良。使用全外显子组测序在先证中进行分子研究。通过Sanger测序确认鉴定的变体的家族分离。
■在先证中发现了两个临床相关的变体：新的从头杂合错义c.931A>G（p。Ser311Gly）在TP63基因中被归类为致病性，纯合无义致病性c.181C>T（p。Arg604Ter）在CNGB3基因中。在姐妹中也发现了相同的纯合CNGB3变异，解释这两种情况下的锥体营养不良。
■整个外显子组测序允许双重分子诊断：从头TP63相关的综合征性异位和家族性CNGB3相关的先天性视锥细胞营养不良。
