ADULT综合征中的睑板腺缺失和锥体营养不良:通过全外显子测序鉴定两个致病基因TP63和CNGB3中的致病变体。

IF 1.2 4区 医学 Q4 GENETICS & HEREDITY
Ophthalmic Genetics Pub Date : 2024-02-01 Epub Date: 2023-05-09 DOI:10.1080/13816810.2023.2206891
Syrine Hizem, Rym Maamouri, Anissa Zaouak, Imen Rejeb, Sana Karoui, Molka Sebai, Houweyda Jilani, Yasmina Elaribi, Sami Fenniche, Monia Cheour, Frédéric Bilan, Lamia Ben Jemaa
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Ophthalmic findings are very common in <i>TP63</i>-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.</p><p><strong>Methods: </strong>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. 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引用次数: 0

摘要

背景:手足外翻(Ectrodactyly)是一种罕见的先天性肢体畸形,其特征是手部和/或足部因缺乏中央突起而出现中间深裂。它可能是孤立的,也可能是多种综合征的一部分。TP63 基因中的杂合子致病变体是导致至少四种与手足外翻相关的罕见人类综合症的原因。其中,ADULT(Acro-Dermato-Ungual-Lacrimal-Tooth)综合征的特征是外胚层发育不良、过度雀斑、指甲发育不良和泪管阻塞,此外还有外畸形和/或联合畸形。在与 TP63 相关的疾病中,眼部病变非常常见,主要是泪腺导管发育不良。EEC3(外生殖器发育不全唇腭裂)综合征中也有睑板腺缺失的记录,但 ADULT 综合征中却没有:我们报告了一例与 ADULT 综合征一致的综合征性外生殖器发育不良病例,该病例还伴有睑板腺发育不全的眼部表现。我们采用全外显子测序技术对该病例进行了分子检测。通过桑格测序确认了所发现变异的家族遗传:结果:在该患者身上发现了两个与临床相关的变异:TP63基因中被归类为致病性的新发杂合错义c.931A > G (p.Ser311Gly),以及CNGB3基因中的同源无义致病性c.1810C > T (p.Arg604Ter)。在妹妹身上也发现了同样的同源CNGB3变异,这也是两个病例中锥体营养不良的原因:结论:全外显子组测序可进行双重分子诊断:新生TP63相关综合征畸形和家族性CNGB3相关先天性锥体营养不良。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Absent meibomian glands and cone dystrophy in ADULT syndrome: identification by whole exome sequencing of pathogenic variants in two causal genes TP63 and CNGB3.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Whole Exome Sequencing allowed dual molecular diagnoses: de novo TP63-related syndromic ectrodactyly and familial CNGB3-related congenital cone dystrophy.

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来源期刊
Ophthalmic Genetics
Ophthalmic Genetics 医学-眼科学
CiteScore
2.40
自引率
8.30%
发文量
126
审稿时长
>12 weeks
期刊介绍: Ophthalmic Genetics accepts original papers, review articles and short communications on the clinical and molecular genetic aspects of ocular diseases.
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