Exome sequencing in four families with neurodevelopmental disorders: genotype–phenotype correlation and identification of novel disease-causing variants in VPS13B and RELN

• Published in: Molecular genetics and genomics : MGG 2024-12, Vol.299 (1), p.55-55, Article 55
• Main Authors: Afridi, Tehseen Ullah Khan, Fatima, Ambrin, Satti, Humayoon Shafique, Akram, Zaineb, Yousafzai, Imran Khan, Naeem, Wajahat Bin, Fatima, Nasreen, Ali, Asmat, Iqbal, Zafar, Khan, Ayaz, Shahzad, Muhammad, Liu, Chunyu, Toft, Mathias, Zhang, Feng, Tariq, Muhammad, Davis, Erica E., Khan, Tahir N.
• Format: Article
• Language: English
• Subjects: Age; Animal Genetics and Genomics; Biochemistry; Bioinformatics; Biomedical and Life Sciences; Cell Adhesion Molecules, Neuronal - genetics; Child; Child, Preschool; Diagnosis; Exome - genetics; Exome Sequencing; Female; Genetic Association Studies - methods; Genetic diversity; Genetic engineering; Genetic Predisposition to Disease; Genomes; Genomics; genotype-phenotype correlation; Genotypes; Hospitals; Human Genetics; Humans; Life Sciences; Male; Medicine; Microbial Genetics and Genomics; Microcephaly; Mutation; Nervous system; Neurodevelopmental disorders; Neurodevelopmental Disorders - genetics; Original Article; Pakistan; Pediatrics; Pedigree; Performance evaluation; peripheral nervous system; Phenotypes; Plant Genetics and Genomics; Structure-function relationships; Vesicular Transport Proteins - genetics
• ISSN: 1617-4615; 1617-4623
• DOI: 10.1007/s00438-024-02149-y

Neurodevelopmental disorders (NDDs) are a clinically and genetically heterogeneous group of early-onset pediatric disorders that affect the structure and/or function of the central or peripheral nervous system. Achieving a precise molecular diagnosis for NDDs may be challenging due to the diverse genetic underpinnings and clinical variability. In the current study, we investigated the underlying genetic cause(s) of NDDs in four unrelated Pakistani families. Using exome sequencing (ES) as a diagnostic approach, we identified disease-causing variants in established NDD-associated genes in all families, including one hitherto unreported variant in RELN and three recurrent variants in VPS13B , DEGS1 , and SPG11 . Overall, our study highlights the potential of ES as a tool for clinical diagnosis.