Detection of RAG mutations and prenatal diagnosis in families presenting with either T–B– severe combined immunodeficiency or Omenn's syndrome

It has been recently shown that mutations in both of the recombination activating genes RAG1 and RAG2 are involved in each of the two different types of severe combined immunodeficiency (SCID) syndromes: T – B – SCID and Omenn's syndrome (OS). The objective of the study was to search for novel mutations in the RAG genes and to offer prenatal diagnosis for families that have been identified as at risk of T – B – SCID or OS. Mutation analyses of polymerase chain reaction products of RAG1 / RAG2 genes were performed in 14 cases (T – B – SCID = 6 and OS = 8). Consanguinity was reported in seven (50%) families. Four missense mutations in the RAG2 gene in six of eight OS patients and in four of six T – B – SCID patients were detected. The C1845T transition leading to a Tre215Ile substitution is a novel mutation. All but one of the patients were homozygous for the detected mutations, possibly reflecting the consanguinity in these families and the relative rarity of the disease‐causing mutations. In addition, three putative polymorphic sites were found. Prenatal diagnosis was offered to seven families, but three of them declined genetic counseling for religious reasons. In the remaining families, four pregnancies were successfully completed, and in one case, the family chose to have an abortion because of a homozygous mutation. Mutations in RAG1 / RAG2 genes were detected in only some of the T – B – SCID or OS patients, and the molecular basis for the remaining cases has yet to be elucidated. Important factors such as religious beliefs need to be considered when offering prenatal diagnosis to certain families.