LPS-responsive beige-like anchor protein (LRBA) encodes widely expressed cytosolic protein which participates in polarized vesicle trafficking. Homozygous loss of function LRBA mutations involve immune deficiency due to the lack of immune regulation as a part of Tregopathies.
We present 49 years old female case with common variable immune deficiency. She has periodic hematuria, dysuria and cough attacks and she gets IVIG treatment regularly. She has background of 11 years of asthma, 3 years of rheumatoid arthritis and hypothyroidism.
We performed immune deficiencies research DNA sequencing panel (264 gene and 5241 amplicons) which concluded with homozygous LRBA mutation (p.Arg722His) at BEACH domain. Mutation is evaluated to be causative and we sequenced mother of the case and two healthy brothers for segregating the mutation. One of the brothers was found to be heterozygous for same mutation whereas mother and other brother were not carrier. We could not be able to sequence her father because he was not alive at time of tests. We hypothetically estimate father to be carrier, but our care remained obscure. We analyzed DNA sample with SNP array that revealed uniparental isodisomy (UPD) of whole chromosome 4.
Whole chromosome uniparental isodisomy is a rare condition. More commonly small chromosomes are involved as a part of unclear trisomy or monosomy rescue process. LRBA deficiency case with partial isodisomy has been reported previously. To our knowledge we report LRBA mutation to became homozygous state due to whole chromosome UPD for the first time.