Case Report: Preserved umbilical cords underscore family histories of inborn errors of immunity

Abstract

A history of susceptibility to infections and a family history of death because of unexplained infections during infancy are helpful in diagnosing inborn errors of immunity (IEIs). However, infections can occur because of various reasons, and determining whether the underlying disease is undoubtedly an IEI is implausible at present. In Japan, preservation of the umbilical cord at birth is customary. Two patients were suspected of having X-linked agammaglobulinemia (XLA); the patients were ultimately diagnosed with XLA based on the history of susceptibility to infections and family histories of deaths of maternal uncles because of infections during infancy. DNA was extracted from umbilical cords that had been preserved for approximately 50 years. The affected children harbored the same Bruton tyrosine kinase (BTK) variants as those detected using the umbilical cord samples of their maternal uncles. Analysis of preserved umbilical cords can help in ascertaining a family history of IEIs.

Keywords: Bruton tyrosine kinase; X-linked agammaglobulinemia; family history; inborn errors of immunity; umbilical cord.

Figure 1

Family pedigrees, flow cytometry, and Sanger sequencing of patients 1 and 2. Family pedigrees of patients 1 (A) and 2 (C). Flow cytometric analysis of Bruton tyrosine kinase (BTK) protein expression in monocytes revealed a decrease in expression levels in patients 1 (B) and 2 (D). Red and blue lines indicate the staining of BTK monoclonal and isotype antibodies, respectively. Numbers indicate the percentages of the BTK-positive cells. Sanger sequencing revealed the presence of BTK variants c.1766A>T and c.530delC in patients 1 (E) and 2 (F), respectively. The mother of patient 2 showed mosaic expression of the BTK protein (D) and BTK gene (F).