REVIEW ARTICLE| Volume 38, ISSUE 3, P169-175, June 2005

Download started.


Kindler surprise: mutations in a novel actin-associated protein cause Kindler syndrome


      Kindler syndrome is an autosomal recessive genodermatosis characterized by acral blistering in neonates and diffuse, progressive poikiloderma in later life. Other clinical features include photosensitivity, premature skin ageing and severe periodontal disease. Two groups have recently shown that the molecular basis of Kindler syndrome is loss of a novel epidermal protein, kindlin-1, encoded by the gene KIND1. Two additional kindlin proteins, kindlin-2 and kindlin-3, have also been described. Kindlin-1 is considered to be a component in the linkage of the actin cytoskeleton to the extracellular matrix and as such is proposed to have both structural and cell-signalling functions. Kindler syndrome is therefore the first skin fragility syndrome due to disruption of the actin–extracellular matrix system.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Dermatological Science
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Kindler T.
        Congenital poikiloderma with traumatic bulla formation and progressive cutaneous atrophy.
        Br J Dermatol. 1954; 66: 104-111
        • Hacham-Zadeh S.
        • Garfunkel A.A.
        Kindler syndrome in two related Kurdish families.
        Am J Med Genet. 1985; 20: 43-48
        • Ban M.
        • et al.
        Kindler's syndrome with recurrence of bullae in the fifth decade.
        Br J Dermatol. 1996; 135: 503-504
        • Shimizu H.
        • et al.
        Immunohistochemical, ultrastructural, and molecular features of Kindler syndrome distinguish it from dystrophic epidermolysis bullosa.
        Arch Dermatol. 1997; 133: 1111-1117
        • Alper J.C.
        • Baden H.P.
        • Goldsmith L.A.
        Kindler's syndrome.
        Arch Dermatol. 1978; 114: 457
        • Al Aboud K.
        • et al.
        Kindler syndrome in a Saudi kindred.
        Clin Exp Dermatol. 2002; 27: 673-676
        • Sharma R.C.
        • et al.
        Kindler syndrome.
        Int J Dermatol. 2003; 42: 727-732
        • Ricketts D.N.
        • et al.
        Kindler syndrome: a rare cause of desquamative lesions of the gingiva.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997; 84: 488-491
        • Suga Y.
        • et al.
        A Japanese case of Kindler syndrome.
        Int J Dermatol. 2000; 39: 284-286
        • Lotem M.
        • et al.
        Kindler syndrome complicated by squamous cell carcinoma of the hard palate: successful treatment with high-dose radiation therapy and granulocyte–macrophage colony-stimulating factor.
        Br J Dermatol. 2001; 144: 1284-1286
        • Haber R.M.
        • Hanna W.M.
        Kindler syndrome. Clinical and ultrastructural findings.
        Arch Dermatol. 1996; 132: 1487-1490
        • Mallipeddi R.
        • et al.
        Dilemmas in distinguishing between dominant and recessive forms of dystrophic epidermolysis bullosa.
        Br J Dermatol. 2003; 149: 810-818
        • Siegel D.H.
        • et al.
        Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin–extracellular-matrix linker protein UNC-112, causes Kindler syndrome.
        Am J Hum Genet. 2003; 73: 174-187
        • Jobard F.
        • et al.
        Identification of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome.
        Hum Mol Genet. 2003; 12: 925-935
        • Uitto J.
        • Pulkkinen L.
        • Christiano A.M.
        Molecular basis of the dystrophic and junctional forms of epidermolysis bullosa: mutations in the type VII collagen and kalinin (laminin 5) genes.
        J Invest Dermatol. 1994; 103: 39S-46S
        • Wehrle-Haller B.
        • Imhof B.
        The inner lives of focal adhesions.
        Trends Cell Biol. 2002; 12: 382-389
        • Chishti A.H.
        • et al.
        The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane.
        Trends Biochem Sci. 1998; 23: 281-282
        • Maffucci T.
        • Falasca M.
        Specificity in pleckstrin homology (PH) domain membrane targeting: a role for a phosphoinositide–protein co-operative mechanism.
        FEBS Lett. 2001; 506: 173-179
        • Rogalski T.M.
        • et al.
        The UNC-112 gene in Caenorhabditis elegans encodes a novel component of cell-matrix adhesion structures required for integrin localization in the muscle cell membrane.
        J Cell Biol. 2000; 150: 253-264
        • Tu Y.
        • et al.
        Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation.
        Cell. 2003; 113: 37-47
        • Boyd R.S.
        • et al.
        Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B.
        Leukemia. 2003; 17: 1605-1612
        • Weinstein E.J.
        • et al.
        URP1: a member of a novel family of PH and FERM domain-containing membrane-associated proteins is significantly over-expressed in lung and colon carcinomas.
        Biochim Biophys Acta. 2003; 1637: 207-216
        • Ashton G.H.
        • et al.
        Recurrent mutations in kindlin-1, a novel keratinocyte focal contact protein, in the autosomal recessive skin fragility and photosensitivity disorder, Kindler syndrome.
        J Invest Dermatol. 2004; 122: 78-83
        • Ashton G.H.
        Kindler syndrome.
        Clin Exp Dermatol. 2004; 29: 116-121


      Sharon J. White graduated from the University of Dundee, Scotland with a BMSc(Honours) in Anatomy in 1993 and a BDS with Honours in 1996. She completed general professional training in 1998 then worked for 3 years as a general dental practitioner in Glasgow, Scotland. In 2001 she returned to Ninewells Hospital, Dundee as a Senior House Officer in Oral Pathology and in 2002 obtained Membership of the Faculty of Dental Surgery (MFDS) of the Royal College of Physicians and Surgeons of Glasgow. She was awarded an MRC Clinical Research Training Fellowship in 2003 and is currently working towards a PhD in Molecular Genetics in the Epithelial Genetics Group, Ninewells, Dundee. She also holds an Honorary Specialist Registrar post in Oral Pathology. Her main interest is oral and maxillofacial pathology, particularly the oral manifestations of hereditary skin disorders.


      W.H. Irwin McLean graduated from The Queen's University of Belfast, Northern Ireland with a BSc(Honours) in Microbiology in 1985 and a PhD in Human Genetics in 1988. He worked as a Research Assistant in Medical Genetics in Belfast from 1985 to 1991 and as a Postdoctoral Fellow in Department of Anatomy and Physiology, University of Dundee, Scotland from 1992 to 1996. He moved to Thomas Jefferson University, Philadelphia, USA in 1996 where he was Associate Professor in Dermatology and Cutaneous Biology until 1998, when he returned to Ninewells Medical School at the University of Dundee as a Wellcome Trust Senior Research Fellow and from 2002, as Professor of Human Genetics. He was awarded a DSc degree from The Queen's University of Belfast in 1999 for his work on inherited skin diseases. He sits on the Editorial boards of the Journal of Investigative Dermatology and Journal of Dermatological Science. His main research interest is understanding the genetics and molecular pathology of hereditary diseases that cause fragility of the epidermis, its appendages and other epithelial tissues. Recently, the emphasis of his work has begun to move away from gene mapping and gene function towards therapy development for inherited skin disorders.