GAPO syndrome: a novel variant in ANTXR1 gene

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.

KEYWORDS:

• GAPO syndrome
• growth retardation
• alopecia
• pseudo-anodontia
• glaucoma
• ANTRX1
• whole exome sequencing (WES)
• in silico analysis

Acknowledgments

The author would like to acknowledge patient’s contributions and consent to clinical examination.

Author’s contribution

MD played key roles in clinical diagnosis, data analysis, and manuscript composition. AV made significant contributions to genetic and in silico analysis and manuscript preparation. VP and MB contributed to imaging and data collection. SS provided valuable expertise in overall case analysis, diagnosis, management, and manuscript quality.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Ethics approval and consent to participate

All subjects under study provided written consent to participate and publication of their data.

Data availability statement

The datasets during and/or analyzed during the current study is available from the corresponding author on reasonable request.

Additional information

Funding

The financial support is provided by Hyderabad Eye Research Foundation and Hyderabad Eye Institute, Hyderabad, India.