Selective disruption of muscle and brain-specific BPAG1 isoforms in a girl with a 6;15 translocation, cognitive and motor delay, and tracheo-oesophageal atresia

-We report on a female child with oesophageal atresia (EA) and psychomotor retardation associated with a ‘‘de novo’’ reciprocal translocation t(6;15)(p11.2;p12). The patient presents a non-progressive encephalopathy, severe motor and mental retardation, and delayed visual maturation. The 6p breakpoint falls within the BPAG1 gene selectively interrupting the two brain- and muscle-specific isoforms. - BPAG1 codes for a hemidesmosomal protein belonging to the plakin family, originally identified as one of the major autoantigens of bullous pemphigoid (BP). Homozygous BPAG1 knock-out mice show neurodegenerative disease and develop progressive ataxia due to the degeneration of the sensory neurons. No mutations for BPAG1 have been reported so far in humans. -We discuss the possibility that BPAG1 haploinsufficiency or abnormal expression may determine the phenotypical abnormalities of our patient.