Analysis of genes encoding laminin beta2 and related proteins in patients with Galloway-Mowat syndrome.
Galloway-Mowat syndrome (GMS) is a rare autosomal recessive disorder characterized by early onset nephrotic syndrome and microcephaly with various anomalies of the central nervous system. GMS likely represents a heterogeneous group of disorders with hitherto unknown genetic etiology. The clinical phenotype to some extent overlaps that of Pierson syndrome (PS), which comprises congenital nephrotic syndrome and distinct ocular abnormalities but which may also include neurodevelopmental deficits and microcephaly. PS is caused by mutations of LAMB2, the gene encoding laminin beta2. We hypothesized that GMS might be allelic to PS or be caused by defects in proteins that interact with laminin beta2. In a cohort of 18 patients with GMS or a GMS-like phenotype we therefore analyzed the genes encoding laminin beta2 (LAMB2), laminin alpha5 (LAMA5), alpha3-integrin (ITGA3), beta1-integrin (ITGB1) and alpha-actinin-4 (ACTN4), but we failed to find causative mutations in these genes. We inferred that LAMA5, ITGA3, ITGB1, and ACTN4 are not directly involved in the pathogenesis of GMS. We excluded LAMB2 as a candidate gene for GMS. Further studies are required, including linkage analysis in families with GMS to identify genes underlying this disease.
Dietrich
Andreas
A
Institute of Human Genetics, University of Erlangen-Nuremberg, Schwabachanlage 10, 91054, Erlangen, Germany.
Matejas
Verena
V
Bitzan
Martin
M
Hashmi
Seema
S
Kiraly-Borri
Cathy
C
Lin
Shuan-Pei
SP
Mildenberger
Eva
E
Hoppe
Bernd
B
Palm
Lars
L
Shiihara
Takashi
T
Steiss
Jens-Oliver
JO
Tsai
Jeng-Daw
JD
Vester
Udo
U
Weber
Stefanie
S
Wühl
Elke
E
Zepf
Kristina
K
Zenker
Martin
M
D000185:Actinin / Q000235:genetics; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D007797:Laminin / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation; D009404:Nephrotic Syndrome / Q000235:genetics*; D013577:Syndrome
C111453:ACTN4 protein, human; D007797:Laminin; D000185:Actinin; C058783:laminin beta2