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Pilarowski-Bjornsson syndrome (PBS) is a rare neurodevelopmental disorder caused by pathogenic variants in the ATP-dependent chromatin remodeler CHD1, typically in an autosomal dominant manner. A single female proband of Saudi descent presented with global developmental delay and developmental dissociation, harboring a heterozygous de novo truncating variant in CHD1 (c.966G>A (p.Trp322Ter)) alongside a co-occurring ASH1L variant (c.1723T>G (p.Ser575Ala)) (PMID:38174187). The CHD1 variant is predicted to result in loss of function in a gene intolerant to haploinsufficiency and recapitulates the genotype spectrum of previously reported missense alleles underlying PBS. No additional affected relatives were reported, and segregation analysis was not possible. Functional characterization of CHD1 across multiple model systems establishes its critical role in chromatin remodeling and transcriptional regulation, although PBS-specific assays for the c.966G>A variant have not been reported. Collectively, this evidence supports a limited but emerging association between heterozygous CHD1 loss-of-function variants and PBS, warranting further case accumulation and mechanistic studies. Key take-home: CHD1 sequencing should be considered in patients with PBS features to confirm diagnosis and guide management.
Gene–Disease AssociationLimitedSingle case report of CHD1 truncating variant in PBS, consistent with prior missense variants ([PMID:38174187]). Genetic EvidenceLimitedOne proband with de novo CHD1 truncating variant (c.966G>A (p.Trp322Ter)) in an autosomal dominant pattern, no segregation data ([PMID:38174187]). Functional EvidenceLimitedGeneral studies demonstrate CHD1’s role in chromatin remodeling but lack PBS-specific functional assays. |