Twin carriers of X-linked agammaglobulinemia (XLA) due to germline mutation in theBtk gene

✍ Scribed by Curtis, Sherill K.; Hebert, Michael D.; Saha, Bratin K.

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 14 KB
• Volume: 90
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/(sici)1096-8628(20000131)90:3<229::aid-ajmg8>3.0.co;2-q

✦ Synopsis

We report on an X-linked agammaglobulinemia (XLA) family in which mothers of two affected cousins were monozygotic twins. We analyzed the Btk gene of several members in three generations of the family by SSCP analysis, DNA sequencing, and RFLP analysis following polymerase chain reaction-amplification of the individual exons. We identified a missense point mutation, G1817C (R562P), in exon 17 of the Btk gene in the affected cousins. The same mutation was also present in both mothers (twin sisters) of the cousins identifying them as carriers. However, the mutation was absent in all other relatives including the grandmother of the cousins (mother of the twin sisters). This strongly suggests that the mutation in the Btk gene had originated in one of the germ lines or in the zygote. This may be the first demonstration of a germ line (or zygotic) mutation in XLA. Am.