Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature

Abstract

Intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP) (MIM#617333) is an autosomal dominant disorder characterized by delayed psychomotor development, intellectual disability (ID), and dysmorphic facial features due to pathogenic variations in the Bromodomain-and PHD Finger-Containing Protein (BRPF1) (MIM#602410) gene. Herein, we report the first Turkish patients with IDDDFP. Additionally, the patients had hematopoietic disorders such as anemia and thrombocytopenia, which have not been previously described in IDDDFP patients.Genetic testing using Whole Exome Sequencing (WES) revealed a novel heterozygous c.1433G > A; p.W478* (NM_004634.3) pathogenic variant on exon 3 of the BRPF1 gene. The patients demonstrated classical features of IDDDFP such as intellectual disability, developmental delay, ptosis, micro and retrognathia, and dysmorphic facial features, in addition to the anemia and thrombocytopenia. Apart from the variant in BRPF1, no additional genomic changes were detected by WES and chromosomal microarray analysis (CMA). Hopefully, our novel report on the hematopoietic anomalies of our patients due to BRPF1 will expand upon the clinical spectrum of IDDDFP, encourage further studies about BRPF1-hematopoietic system relations, and affect the diagnostic and therapeutic schemes of hematopoietic system disorders.

Genetic analysis of BRPF1 exon deletion variant causing intellectual developmental disorder with dysmorphic facies and ptosis in a Chinese family

“…Notably, only one case involving a 3-month-old infant with feverinduced multiple seizures has been documented, similar to the seizure characteristics in our proband, suggesting the involvement of BRPF1 in the mechanism of epilepsy [10]. The primary reported variants comprised frameshift (47%, 16/34), nonsense (26%, 9/34), and three deletion (9%) variants, suggesting haploinsufficiency of BRPF1 as a pathological mechanism [3,[5][6][7][8][9][10][11][12][13]. However, phenotypic variations exist among affected individuals within the same family.…”

“…Additionally, some patients exhibit skeletal deformities (72%, 31/43), including hand (brachydactyly and brachymetacarpia) and foot (clubfoot or syndactyly) differences. However, a minority of patients with IDDDFP experience seizures (21%, 9/43) and structural brain abnormalities (50%, 10/20), often characterized by abnormal white matter signals under MRI and corpus callosum thinning [3,[5][6][7][8][9][10][11][12][13]. The affected family members in our report exhibited typical facial dysmorphisms of IDDDFP.…”

“…Fewer than 50 cases of IDDDFP have been reported, highlighting the scarcity of essential research data regarding the correlation between disease phenotypes and genotypes [3,[5][6][7][8][9][10][11][12][13]. In this study, we present a case involving a Chinese family exhibiting typical IDDDFP features, with the proband also presenting with infantile epilepsy and developmental delay.…”