Gain-of-function IKBKB mutation causes human combined immune deficiency

A nonsense mutation in IKBKB causes combined immunodeficiency.

Identification of the molecular etiologies of primary immunodeficiencies has led to important insights into the development and function of the immune system. We report here the cause of combined immunodeficiency in 4 patients from 2 different consanguineous Qatari families with similar clinical and immunologic phenotypes. The patients presented at an early age with fungal, viral, and bacterial...

Med12 gain-of-function mutation causes leiomyomas and genomic instability.

Uterine leiomyomas are benign tumors that can cause pain, bleeding, and infertility in some women. Mediator complex subunit 12 (MED12) exon 2 variants are associated with uterine leiomyomas; however, the causality of MED12 variants, their genetic mode of action, and their role in genomic instability have not been established. Here, we generated a mouse model that conditionally expresses a Med12...

Severe combined immune deficiency syndrome.

OBJECTIVE To determine the clinico-demographic features and laboratory parameters of children with severe combined immunodeficiency (SCID). STUDY DESIGN Case series. PLACE AND DURATION OF STUDY Department of Paediatrics and Child Health, the Aga Khan University, Karachi, from July 2006 to July 2011. METHODOLOGY Thirteen infants who were discharged with a diagnosis of SCID were inducted in...

Deficiency of Innate and Acquired Immunity Caused by an IKBKB Mutation.

BACKGROUND Severe combined immunodeficiency (SCID) comprises a heterogeneous group of heritable deficiencies of humoral and cell-mediated immunity. Many patients with SCID have lymphocyte-activation defects that remain uncharacterized. METHODS We performed genetic studies in four patients, from four families of Northern Cree ancestry, who had clinical characteristics of SCID, including early ...

A Gain-of-Function Mutation of the SCN5A Gene Causes Exercise-Induced Polymorphic Ventricular Arrhythmias