Archer Jessica, Goh Shuxiang, Miteff Christina, O'Donnell Sheridan, Park Kristen, Goel Himanshu
Hunter Genetics, Waratah, NSW 2298, Australia.
School of Women and Children's Health, University of New South Wales, Sydney, NSW 2052, Australia.
Genes (Basel). 2025 Aug 18;16(8):972. doi: 10.3390/genes16080972.
encodes a cell adhesion molecule initially implicated in atrioventricular septal defects (AVSDs). More recently, biallelic variants have been associated with syndromic and non-syndromic neurodevelopmental disorders (NDDs). We describe three individuals from unrelated families with compound heterozygous variants, identified through exome sequencing. Clinical and genetic data were reviewed to delineate shared and divergent features. All three patients presented with developmental delay, intellectual disability, seizures, hypotonia, and dysmorphic facial features. Patient 1 and patient 2 carried a recurrent variant combination previously reported in five individuals, while Patient 3 harboured the recurrent frameshift p.(Gln320Argfs*25) variant in trans with a novel missense variant. The milder clinical course of patient 3 highlights phenotypic heterogeneity. Notably, none of the patients had cardiac anomalies or immunological abnormalities, further expanding the clinical spectrum associated with . Our findings reinforce genotype-phenotype correlations and provide additional evidence that biallelic variants underlie a distinct autosomal recessive neurodevelopmental disorder, broadening both the phenotypic and genetic spectrum of this emerging syndrome.
编码一种最初与房室间隔缺损（AVSDs）有关的细胞粘附分子。最近，双等位基因变异已与综合征性和非综合征性神经发育障碍（NDDs）相关联。我们描述了通过外显子组测序鉴定出的来自三个无关家庭的具有复合杂合变异的个体。对临床和遗传数据进行了回顾，以勾勒出共同特征和不同特征。所有三名患者均表现出发育迟缓、智力残疾、癫痫发作、肌张力减退和面部畸形特征。患者1和患者2携带了先前在五名个体中报道过的复发性变异组合，而患者3携带了复发性移码p.(Gln320Argfs*25)变异，与一个新的错义变异呈反式。患者3较轻的临床病程突出了表型异质性。值得注意的是，所有患者均无心脏异常或免疫异常，进一步扩大了与之相关的临床谱。我们的研究结果强化了基因型-表型相关性，并提供了额外证据表明双等位基因变异是一种独特的常染色体隐性神经发育障碍的基础，拓宽了这种新兴综合征的表型和遗传谱。
