G2019S Mutation of Leucine-Rich Repeat Kinase 2 Is a Cause of Lewy Body Dementia in Patients With North African Ancestors.

Background: Mutations in the LRRK2 gene are the most common genetic cause of Parkinson disease but are believed to play no significant role in Lewy body disease (LBD).

Objectives: As the frequency of G2019S LRRK2 mutation is extremely high in North African patients with Parkinson disease, we postulate that the high prevalence of LBD in North Africa might be due to the same mutation because LBD and Parkinson disease share many clinical, pathological, and genetic features.

Methods: We screened patients with LBD or prodromal LBD for the G2019S mutation of LRRK2.

Diagnosis and clinical relevance of co-inheritance of haemoglobin D-Punjab/β+-thalassemia traits in an immigrant Afghan family.

We report on a Pashtun family affected by haemoglobin D-Punjab/β+-thalassemia to increase the awareness of the increasing prevalence of haemoglobinopathies among primary care physicians. We highlight the diagnostic approach of these conditions and the benefits of genetic counselling.

Heterogeneous colonic content: A prenatal sonographic manifestation of lysinuric protein intolerance.

We report a fetus with heterogeneous colonic content, an isolated sonographic prenatal sign of lysinuric protein intolerance, a very rare metabolic disease. Familial genetic enquiries confirmed heterozygote mutation in the implicated gene in parents. The prenatal diagnosis led to neonatal dietary adaptation and avoided acute complications.

Development by Genetic Immunization of Monovalent Antibodies Against Human Vasoactive Intestinal Peptide Receptor 1 (VPAC1), New Innovative, and Versatile Tools to Study VPAC1 Receptor Function.

Multi-membrane spanning proteins, such as G protein-coupled receptors (GPCRs) and ion channels, are extremely difficult to purify as native proteins. Consequently, the generation of antibodies that recognize the native conformation can be challenging. By combining genetic immunization, phage display, and biopanning, we identified a panel of monovalent antibodies (nanobodies) targeting the vasoactive intestinal peptide receptor 1 (VPAC1) receptor.

Development by Genetic Immunization of Monovalent Antibodies (Nanobodies) Behaving as Antagonists of the Human ChemR23 Receptor.

The generation of Abs that recognize the native conformation of G protein-coupled receptors can be a challenging task because, like most multimembrane-spanning proteins, they are extremely difficult to purify as native protein. By combining genetic immunization, phage display, and biopanning, we identified two functional monovalent Abs (nanobodies) targeting ChemR23. The two nanobodies (CA4910 and CA5183) were highly specific for the human receptor and bind ChemR23 with moderate affinity.