The BCAP31 gene (MIM 300398) is located at Xq28 and encodes B-cell-receptor-associated protein 31 (BAP31), a ubiquitous 31 kDa chaperone protein highly expressed in neuron. It is the most abundant of endoplasmic reticulum (ER) membrane proteins and plays a role in regulation of apoptosis, protein transport and degradation. BAP31 has a role in the export of secreted proteins and their targeting to the ER-associated-degradation pathway (ERAD). BAP31 also serves as a cargo receptor for the export of transmembrane proteins.
Less than 30 patients have been described in the literature as of dec 31st, 2021. The incidence of the disorder is unknown.
The patients present severe to profound developmental delay (DD) or intellectual disability (ID), dystonia, seizures, sensorineural hearing loss (SNHL) and central myelination delay which defined the DDCH syndrome (for Deafness, Dystonia and Cerebral Hypomyelination, MIM 300475). Exceptionally, the phenotype can be milder with patients acquiring partial language and basic academic skills. Symptomatic female carriers may suffer from hearing loss and/or DD/ID. Asymptomatic female carriers with somatic mosaicism have been described.
Liver enzymes are elevated in half of the reported patients, either permanently or intermittently, sometimes during febrile episodes. Patients with pathogenic BCAP31 variants/intragenic deletions generally did not display cholestasis or hepatic failure.
BCAP31