POSTERS
genotype-phenotype correlations in a large cohort of patients with nicolaides-baraitser syndrome (NCBRS).
Nicolaides-Baraitser syndrome is a rare autosomal dominant disorder caused by variants in the SMARCA2 gene, which encodes the core catalytic subunit of the SWI/SNF chromatin remodeling complex. This complex is critical for regulating gene expression, and disruptions can lead to a wide spectrum of clinical manifestations, including neurological, facial, and skeletal abnormalities. In this study, we aim to understand how genetic variants shape these diverse phenotypes, which is a crucial step toward improving both diagnosis and patient management.
We analysed clinical and genetic data from 162 patients, including 80 novel cases, with approximately 60% of the cases are male patient. We observed considerable phenotypic variability among the patients in our cohort. Intellectual disability ranged from mild to severe and was frequently accompanied by other neurodevelopmental impairments, such as absent or delayed speech, ASD, or ADHD. Seizure presentation also varied, with many individuals exhibiting multiple seizure types. Distinct facial dysmorphisms were noted in all individuals, except 2 cases. Sparse hair, orofacial anomalies, and dental anomalies issues emerged as key features, and over half of the patients presented with at least two or three of these primary features. Skeletal abnormalities were also observed, including scoliosis and prominent phalanges or interphalangeal joints, with most patients displaying one or two of these features. Overall, the severity of these clinical characteristics differed markedly across the cohort.
The majority of the identified variants were missense variants (109), with 9 of them are large deletion. These mostly located within the SNF2 ATPase domain, which is a region that critical for its catalytic function. Notably, 18 of the identified variants are novel variants that have never been reported before.
Our work highlights the complexity and diversity of clinical presentations in NCBRS and underscores the importance of detailed genetic analysis. By identifying patterns in genotype and phenotype correlations, we aim to improve diagnostic accuracy and develop more personalised management strategies for the affected individuals.
We would like to thank all the authors for their incredible work and dedication to this important research.
Poster was presented at the BPNA conference, January 2025 in Oxford UK by our esteemed SAB Co-Chair, Professor Paola Nicolaides alongside Renee Lin from The Neurogenetics Lab UCL ION.
We analysed clinical and genetic data from 162 patients, including 80 novel cases, with approximately 60% of the cases are male patient. We observed considerable phenotypic variability among the patients in our cohort. Intellectual disability ranged from mild to severe and was frequently accompanied by other neurodevelopmental impairments, such as absent or delayed speech, ASD, or ADHD. Seizure presentation also varied, with many individuals exhibiting multiple seizure types. Distinct facial dysmorphisms were noted in all individuals, except 2 cases. Sparse hair, orofacial anomalies, and dental anomalies issues emerged as key features, and over half of the patients presented with at least two or three of these primary features. Skeletal abnormalities were also observed, including scoliosis and prominent phalanges or interphalangeal joints, with most patients displaying one or two of these features. Overall, the severity of these clinical characteristics differed markedly across the cohort.
The majority of the identified variants were missense variants (109), with 9 of them are large deletion. These mostly located within the SNF2 ATPase domain, which is a region that critical for its catalytic function. Notably, 18 of the identified variants are novel variants that have never been reported before.
Our work highlights the complexity and diversity of clinical presentations in NCBRS and underscores the importance of detailed genetic analysis. By identifying patterns in genotype and phenotype correlations, we aim to improve diagnostic accuracy and develop more personalised management strategies for the affected individuals.
We would like to thank all the authors for their incredible work and dedication to this important research.
Poster was presented at the BPNA conference, January 2025 in Oxford UK by our esteemed SAB Co-Chair, Professor Paola Nicolaides alongside Renee Lin from The Neurogenetics Lab UCL ION.
