GAPO syndrome: a novel variant in ANTXR1 gene.

IF 1.2 4区 医学 Q4 GENETICS & HEREDITY
Ophthalmic Genetics Pub Date : 2024-08-01 Epub Date: 2024-05-01 DOI:10.1080/13816810.2024.2345879
Manikanta Damagatla, Anshuman Verma, Venkatesh Pochaboina, Manju Bhate, Sirisha Senthil
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引用次数: 0

Abstract

Background: GAPO syndrome is a rare autosomal recessive disorder characterized by the acronym of growth retardation, alopecia, pseudo-anodontia and progressive optic atrophy. While the genetic alteration of the ANTXR1 gene has been known for its cause, the full range of its clinical and genetic manifestations is not well explored due to the syndrome's extreme rarity.

Materials/methods: We report two children born to a non-consanguineous parent in India with classical features of GAPO syndrome. The whole exome sequencing analysis (WES) was performed in both siblings, and the parent's genetic and clinical status was determined. The identified variation was characterized in silico using homology-based protein modelling.

Results: In WES analysis, a homozygous ANTXR1 gene indel variant c. 151_152 + 2delAAGT (p.Lys51fs) was identified in both siblings. The parents were identified as the carriers of the ANTXR1 variant. Additionally, they also displayed mild GAPO-related facial and glaucomatous features. In silico analysis and homology-based ANTXR1 protein structure illustrate a frameshift and the subsequent premature truncation of the protein.

Conclusions: Our reports contribute to the comprehension of GAPO syndrome within the Indian context describing an ANTXR1 novel variant causing premature protein truncation. WES-based genetic testing can significantly aid in expertly diagnosing GAPO syndrome. In the present case scenario, a variable penetrance of ANTXR1 variation was acknowledged as the carrier parents also had a mild degree of GAPO-related features. Future reports that include parental clinical diagnosis can offer further insights in this context.

GAPO综合征:ANTXR1基因的一种新型变异。
背景:GAPO 综合征是一种罕见的常染色体隐性遗传疾病,其特征是生长迟缓、脱发、假性无牙症和进行性视神经萎缩。虽然 ANTXR1 基因的遗传改变已是病因,但由于该综合征极为罕见,其临床和遗传表现的全面性尚未得到很好的探讨:我们报告了两名印度非近亲所生的儿童,他们具有 GAPO 综合征的典型特征。我们对两兄妹进行了全外显子组测序分析(WES),并确定了父母的遗传和临床状况。利用基于同源性的蛋白质建模技术对所发现的变异进行了硅学表征:在 WES 分析中,在两兄妹中都发现了同源的 ANTXR1 基因 indel 变异 c. 151_152 + 2delAAGT (p.Lys51fs)。父母被确定为 ANTXR1 变异携带者。此外,他们还表现出与 GAPO 相关的轻度面部和青光眼特征。硅学分析和基于同源性的 ANTXR1 蛋白结构显示了该蛋白的框架移位和随后的过早截断:我们的报告有助于理解印度背景下的 GAPO 综合征,描述了 ANTXR1 新型变体导致蛋白质过早截短。基于 WES 的基因检测对 GAPO 综合征的专业诊断有很大帮助。在本病例中,ANTXR1 变异的可变渗透性得到了认可,因为携带者的父母也有轻度的 GAPO 相关特征。未来包括父母临床诊断在内的报告可对此提供进一步的见解。
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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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