title: Expression of the nonmuscle myosin heavy chain IIA in the human kidney and screening for MYH9 mutations in Epstein and Fechtner syndromes.
abstract: Mutations in the MYH9 gene, which encodes the nonmuscle myosin heavy chain IIA, have been recently reported in three syndromes that share the association of macrothrombocytopenia (MTCP) and leukocyte inclusions: the May-Hegglin anomaly and Sebastian and Fechtner syndromes. Epstein syndrome, which associates inherited sensorineural deafness, glomerular nephritis, and MTCP without leukocyte inclusions, was shown to be genetically linked to the same locus at 22q12.3 to 13. The expression of MYH9 in the fetal and mature human kidney was studied, and the 40 coding exons of the gene were screened by single-strand conformation polymorphism in 12 families presenting with the association of MTCP and nephropathy. MYH9 is expressed in both fetal and mature kidney. During renal development, it is expressed in the late S-shaped body, mostly in its lower part, in the endothelial and the epithelial cell layers. Later, as well as in mature renal tissue, MYH9 is widely expressed in the kidney, mainly in the glomerulus and peritubular vessels. Within the glomerulus, MYH9 mRNA and protein are mostly expressed in the epithelial visceral cells. Four missense heterozygous mutations that are thought to be pathogenic were found in five families, including two families with Epstein syndrome. Three mutations were located in the coiled-coil rod domain of the protein, and one was in the motor domain. Two mutations (E1841K and D1424N) have been reported elsewhere in families with May-Hegglin anomaly. The two others (R1165L and S96L) are new mutations, although one of them affects a codon (R1165), found elsewhere to be mutated in Sebastian syndrome.
authors.affiliation: *Inserm U 423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Service de Néphrologie, Hôpital Necker, Paris, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Arrondel
authors.affiliation: *Inserm U 423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Service de Néphrologie, Hôpital Necker, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vodovar
authors.affiliation: *Inserm U 423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Service de Néphrologie, Hôpital Necker, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Knebelmann
authors.affiliation: *Inserm U 423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Service de Néphrologie, Hôpital Necker, Paris, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Grünfeld
authors.affiliation: *Inserm U 423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Service de Néphrologie, Hôpital Necker, Paris, France.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gubler
authors.affiliation: *Inserm U 423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Service de Néphrologie, Hôpital Necker, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.affiliation: *Inserm U 423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Service de Néphrologie, Hôpital Necker, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Heidet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D000595:Amino Acid Sequence / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000502:physiology; D015870:Gene Expression; D005820:Genetic Testing; D005921:Glomerulonephritis / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D020033:Protein Isoforms / Q000235:genetics; D013577:Syndrome; D013921:Thrombocytopenia / Q000235:genetics*
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D020033:Protein Isoforms; D018995:Myosin Heavy Chains