Sirica Roberto, Ottaiano Alessandro, Brasi Daniele De, Marcella Simone, Acquaviva Fabio, Ianniello Monica, Petrillo Nadia, De Angelis Valentina, Ruggiero Raffaella, D'Angelo Rossana, Evangelista Eloisa, Fico Antonio, Savarese Giovanni
AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, 80013 Casalnuovo di Napoli, Italy.
Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale", Via Mariano Semmola, 80131 Napoli, Italy.
Genes (Basel). 2025 Apr 29;16(5):519. doi: 10.3390/genes16050519.
Ectodermal dysplasia (ED) encompasses a heterogeneous group of genetic disorders affecting ectoderm-derived structures such as hair, teeth, nails, and sweat glands. Among these, variants in (Thrombospondin-type laminin G domain and epilepsy-associated repeats) have been implicated in autosomal recessive ED type 14 (OMIM 618180), predominantly manifesting with dental anomalies and hair dysplasia. However, the mutational spectrum of remains incompletely characterized.
Two female siblings (ID#1 and ID#4) were clinically evaluated for ED. Genetic analysis, including next-generation sequencing (NGS) and Sanger validation, was conducted to identify variants. A segregation study confirmed inheritance patterns within the family.
Both affected siblings exhibited hallmark features of -related ED14, including oligodontia with dysmorphic, pointed maxillary central incisors. Hair thinning and cutaneous angiomas were predominant in ID#4. Genetic analysis identified two compound heterozygous variants in : c.543-1G>A, a splice-site variant likely to disrupt mRNA processing, and NM_144991.2:c.1251G>C(p.Gln417His), a missense variant with predicted deleterious effects. Segregation analysis confirmed maternal and paternal inheritance of the respective variants. A third sibling, ID#5, was identified as a heterozygous carrier without clinical manifestations.
This study contributes to the expanding understanding of -related ED14 by providing novel genotype-phenotype correlations.
外胚层发育不良（ED）是一组异质性的遗传疾病，影响外胚层衍生结构，如头发、牙齿、指甲和汗腺。其中，（血小板反应蛋白型层粘连蛋白G结构域和癫痫相关重复序列）的变异与常染色体隐性遗传性14型外胚层发育不良（OMIM 618180）有关，主要表现为牙齿异常和毛发发育异常。然而，的突变谱仍未完全明确。
对两名女性同胞（ID#1和ID#4）进行外胚层发育不良的临床评估。进行了包括下一代测序（NGS）和桑格验证在内的基因分析，以鉴定变异。分离研究证实了家族内的遗传模式。
两名受影响的同胞均表现出与相关的ED14的标志性特征，包括少牙症伴上颌中切牙畸形、尖锐。ID#4主要表现为头发稀疏和皮肤血管瘤。基因分析在中鉴定出两个复合杂合变异：c.543-1G>A，一个可能破坏mRNA加工的剪接位点变异，以及NM_144991.2:c.1251G>C（p.Gln417His），一个具有预测有害效应的错义变异。分离分析证实了各自变异的母系和父系遗传。第三名同胞ID#5被鉴定为无临床表现的杂合携带者。
本研究通过提供新的基因型-表型相关性，有助于扩大对相关ED14的认识。
