# Investigating the Role of B9D1 in Meckel–Gruber Syndrome: A Case Report and Comprehensive Literature Review

## TL;DR

This paper reports a prenatal case of Meckel–Gruber syndrome caused by a B9D1 gene variant and reviews related literature to highlight the importance of early diagnosis and genetic testing.

## Contribution

The study confirms the pathogenicity of a specific B9D1 variant and emphasizes the role of prenatal genetic testing in managing MKS.

## Key findings

- A homozygous B9D1 c.151T>C variant was identified in a prenatal case with MKS-like features.
- The variant was inherited from healthy parents, supporting its pathogenic role in the syndrome.
- Timely prenatal diagnosis and genetic testing are critical for reproductive decision-making in MKS.

## Abstract

Meckel–Gruber syndrome (MKS) is a rare autosomal recessive lethal ciliopathy, characterized by occipital encephalocele, cystic kidneys, and postaxial polydactyly, caused by mutations in different genes. Its significant genetic heterogeneity along with its clinical overlap with other ciliopathies makes early diagnosis essential for clinical management, accurate genetic counseling, and informing future reproductive decisions. Objectives: This study aims to describe a prenatally diagnosed case carrying a homozygous B9D1 variant and to examine the current literature on all variants reported in this gene associated with MKS. Methods: We comprehensively review the current literature on pathogenic B9D1 variants implicated in this syndrome. Additionally, we describe a case, presenting multiple congenital anomalies suggestive of MKS, genetically diagnosed by clinical exome sequencing on chorionic villi. Results: Occipital encephalocele and polycystic kidneys were revealed via ultrasound, thus suggesting MKS. Genetic testing identified the homozygous c.151T>C (p.Ser51Pro) variant in the B9D1 gene, inherited from healthy parents. Conclusions: This case supports the pathogenicity of the homozygous B9D1 c.151T>C variant and underscores the importance of timely prenatal assessment and targeted genetic testing for the detection of MKS risk in heterozygous subjects, enabling appropriate pregnancy management and informed reproductive choices.