Identification of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome.
Kindler syndrome is a rare autosomal-recessive genodermatosis characterized by bullous poikiloderma with photosensitivity. We report the localization to chromosome 20p12.3 by homozygosity mapping and the identification of a new gene, which we propose to name kindlerin. We found four different homozygous mutations in four consanguineous families from North Africa and Senegal; three are expected to lead to premature stop codons and truncated proteins and the fourth involves a splice site. We were unable to identify a mutation in kindlerin in a fifth consanguineous family from Algeria with a similar phenotype and in which the patient was homozygous for the markers in the 20p12.3 interval. The kindlerin protein contains several domains which are shared by a diverse group of peripheral membrane proteins that function as membrane-cytoskeleton linkers: two regions homologous to band 4.1 domain of which one includes a FERM domain with a NPKY sequence motif, and a third region with a PH or pleckstrin homology domain. Kindlerin might be involved in the bidirectional signaling between integrin molecules in the membrane and the cytoskeleton, and could be involved in cell adhesion processes via integrin signaling.
Jobard
Florence
F
Centre National de Génotypage, Evry, France.
Bouadjar
Bakar
B
Caux
Frédéric
F
Hadj-Rabia
Smail
S
Has
Christina
C
Matsuda
Fumi
F
Weissenbach
Jean
J
Lathrop
Mark
M
Prud'homme
Jean-François
JF
Fischer
Judith
J
D000293:Adolescent; D000328:Adult; D001798:Blood Proteins / Q000235:genetics*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins; D010750:Phosphoproteins / Q000235:genetics*; D010787:Photosensitivity Disorders / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012871:Skin Diseases / Q000235:genetics*; D013577:Syndrome
D001798:Blood Proteins; D016326:Extracellular Matrix Proteins; C475301:FERMT1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; C039077:platelet protein P47