PIGF deficiency causes a phenotype overlapping with DOORS syndrome

Phenotype–genotype complexities: opening DOORS

The escalating pace of molecular genetic discoveries in neurological diseases is repeatedly providing surprises that challenge our ability to match phenotype and genotype. With the current transition of whole-exome sequencing from the laboratory to clinical use, the ability to understand and interpret molecular-level data becomes ever more important. The classic view of one gene encoding one pr...

Leukocyte adhesion deficiency. Aberrant splicing of a conserved integrin sequence causes a moderate deficiency phenotype.

Leukocyte adhesion deficiency (LAD) is a heritable deficiency of the LFA-1, Mac-1, p150,95 family of leukocyte alpha beta heterodimers (the leukocyte integrins). We have studied the defect in patients who synthesize an aberrantly small form of the beta subunit common to all three proteins. S1 nuclease protection showed the presence of a 90-nucleotide mismatch in RNA from patients and relatives,...

An Overlapping Syndrome of Allergy and Immune Deficiency in Children

Recurrent airway inflammations in children are an important clinical problem in pediatric practice. An essential challenge is differentiation between allergic background and immune deficiency, which is a difficult task taking into consideration individual predisposition to atopy, immune system maturation in the early childhood, as well as exposition to environmental allergens and microbial anti...

A FSH-Secreting Pituitary Macroadenoma Causing A Testosterone Deficiency Syndrome

Increased Protein Stability of CDKN1C Causes a Gain-of-Function Phenotype in Patients with IMAGe Syndrome

Mutations in the proliferating cell nuclear antigen (PCNA)-binding domain of the CDKN1C gene were recently identified in patients with IMAGe syndrome. However, loss of PCNA binding and suppression of CDKN1C monoubiquitination by IMAGe-associated mutations hardly explain the reduced-growth phenotype characteristic of IMAGe syndrome. We demonstrate here that IMAGe-associated mutations in the CDKN...