B ernard– S oulier syndrome caused by a hemizygous GPIb β mutation and 22q11.2 deletion

Background B ernard– S oulier syndrome ( BSS ) is a rare autosomal recessive bleeding disorder characterized by giant platelets, thrombocytopenia, and a prolonged bleeding time, which is caused by homozygous mutations in the GPIb α, GPIb β, or GPIX genes. The 22q11.2 deletion syndrome (22q11.2 DS ) is caused by a microdeletion on chromosome 22, which includes the GPIb β gene, and is characterized by abnormal development of the pharyngeal apparatus and heart. Thus, patients with 22q11.2 DS are obligate carriers for BSS . Methods We evaluated two infants with BSS and performed the genetic analysis of the GPIb α, GPIb β, or GPIX genes, and investigated the segregation of the mutation within the families. The status of the 22q11.2 deletion was examined by fluorescence in situ hybridization and single‐nucleotide polymorphism array copy number analysis. Results DNA sequencing analysis revealed that the infants were compound heterozygous for a hemizygous mutation in the GPIb β gene (p. T rp148 X and p. L eu97 P he, respectively) and 22q11.2 deletion in the other chromosome. Both infants had the common 3 M b 22q11.2 deletion but did not show major phenotypic features of 22q11.2 DS , such as developmental delay, cardiac defects, dysmorphic facial features, palatal anomalies, hypocalcemia, and immune deficiency. The 22q11.2 DS would not have become clear if detailed molecular genetic analyses of BSS had not been performed. Conclusions Our cases illustrate that a suspicion of 22q11.2 deletion is warranted in pediatric BSS patients with a mutation in the GPIb β gene, even without remarkable symptoms.