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Cutis Laxa

  • Miski MohamedEmail author
  • Michiel Voet
  • Thatjana Gardeitchik
  • Eva Morava
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 802)

Abstract

Cutis laxa is an inherited or acquired disease characterized by redundant, sagging and inelastic skin. In inherited cutis laxa an abnormal synthesis of extracellular matrix proteins occurs due to genetic defects coding for diverse extracellular matrix components. Recently, different inborn errors of metabolism have been found to be associated with cutis laxa as well. In some of these metabolic conditions the pathomechanism of cutis laxa remains unknown. Cutis laxa can be inherited in an autosomal dominant, autosomal recessive and X-linked recessive inheritance pattern. Besides the skin abnormalities, in most inherited forms multiple organ systems are involved, leading to a severe, in some forms even lethal, multisystem disorder. To date no effective treatment is available for cutis laxa. This chapter focuses on inherited forms of cutis laxa, offering a practical guideline for clinicians, biochemist and geneticist to diagnose and differentiate between the different forms of cutis laxa, and providing a concise theoretical reference.

Keywords

Autosomal recessive cutis laxa (ARCL) ARCL type 1A (ARCL1A; MIM 219100) FBLN5 (MIM 604580) ARCL type 1B (ARCL1B; MIM 614437) EFEMP2 or FBLN4 (MIM 604633) ARCL1C Urban-Rifkin-Davis Syndrome (URDS; MIM 613177) LTBP4 (MIM 604710) ARCL type 2 Debré-type cutis laxa (ARCL2A; MIM 219200) 

References

  1. 1.
    Morava E, Guillard M, Lefeber DJ, Wevers RA (2009) Autosomal recessive cutis laxa syndrome revisited. Eur J Hum Genet 17(9):1099–1110Google Scholar
  2. 2.
    Gardeitchik T, Morava E (2013) Cutis Laxa. In: Maloy S, Hughes K (eds) Brenner’s encyclopedia of genetics, vol 2, 2nd edn. Academic, San Diego, pp 254–257CrossRefGoogle Scholar
  3. 3.
    Kaler SG (1998) Metabolic and molecular bases of Menkes disease and occipital horn syndrome. Pediatr Dev Pathol 1(1):85–98PubMedCrossRefGoogle Scholar
  4. 4.
    Kaler SG (2011) ATP7A-related copper transport diseases-emerging concepts and future trends. Nat Rev Neurol 7(1):15–29PubMedCrossRefGoogle Scholar
  5. 5.
    Proud VK, Mussell HG, Kaler SG, Young DW, Percy AK (1996) Distinctive Menkes disease variant with occipital horns: delineation of natural history and clinical phenotype. Am J Med Genet 65(1):44–51PubMedCrossRefGoogle Scholar
  6. 6.
    Urban Z, Gao J, Pope FM, Davis EC (2005) Autosomal dominant cutis laxa with severe lung disease: synthesis and matrix deposition of mutant tropoelastin. J Invest Dermatol 124(6):1193–1199PubMedCrossRefGoogle Scholar
  7. 7.
    Damkier A, Brandrup F, Starklint H (1991) Cutis laxa: autosomal dominant inheritance in five generations. Clin Genet 39(5):321–329PubMedCrossRefGoogle Scholar
  8. 8.
    Tassabehji M, Metcalfe K, Hurst J, Ashcroft GS, Kielty C, Wilmot C, Donnai D, Read AP, Jones CJ (1998) An elastin gene mutation producing abnormal tropoelastin and abnormal elastic fibres in a patient with autosomal dominant cutis laxa. Hum Mol Genet 7(6):1021–1028PubMedCrossRefGoogle Scholar
  9. 9.
    Zhang MC, He L, Giro M, Yong SL, Tiller GE, Davidson JM (1999) Cutis laxa arising from frameshift mutations in exon 30 of the elastin gene (ELN). J Biol Chem 274(2):981–986PubMedCrossRefGoogle Scholar
  10. 10.
    Metcalfe K, Rucka AK, Smoot L, Hofstadler G, Tuzler G, McKeown P, Siu V, Rauch A, Dean J, Dennis N, Ellis I, Reardon W, Cytrynbaum C, Osborne L, Yates JR, Read AP, Donnai D, Tassabehji M (2000) Elastin: mutational spectrum in supravalvular aortic stenosis. Eur J Hum Genet 8(12):955–963PubMedCrossRefGoogle Scholar
  11. 11.
    Markova D, Zou YQ, Ringpfeil F, Sasaki T, Kostka G, Timpl R, Uitto J, Chu ML (2003) Genetic heterogeneity of cutis laxa: a heterozygous tandem duplication within the fibulin-5 (FBLN5) gene. Am J Hum Genet 72(4):998–1004PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J (1993) Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase (Vol 3, Pg 7, 1993). Nat Genet 3(3):273Google Scholar
  13. 13.
    Chelly J, Tumer Z, Tonnesen T, Petterson A, Ishikawabrush Y, Tommerup N, Horn N, Monaco AP (1993) Isolation of a candidate gene for Menkes disease that encodes a potential heavy-metal binding-protein. Nat Genet 3(1):14–19PubMedCrossRefGoogle Scholar
  14. 14.
    Mercer JF, Livingston J, Hall B, Paynter JA, Begy C, Chandrasekharappa S, Lockhart P, Grimes A, Bhave M, Siemieniak D et al (1993) Isolation of a partial candidate gene for Menkes disease by positional cloning. Nat Genet 3(1):20–25PubMedCrossRefGoogle Scholar
  15. 15.
    Gu YH, Kodama H, Murata Y, Mochizuki D, Yanagawa Y, Ushijima H, Shiba T, Lee CC (2001) ATP7A gene mutations in 16 patients with Menkes disease and a patient with occipital horn syndrome. Am J Med Genet 99(3):217–222PubMedCrossRefGoogle Scholar
  16. 16.
    Loeys B, Van Maldergem L, Mortier G, Coucke P, Gerniers S, Naeyaert JM, De Paepe A (2002) Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa. Hum Mol Genet 11(18):2113–2118PubMedCrossRefGoogle Scholar
  17. 17.
    Claus S, Fischer J, Megarbane H, Megarbane A, Jobard F, Debret R, Peyrol S, Saker S, Devillers M, Sommer P, Damour O (2008) A p.C217R mutation in fibulin-5 from cutis laxa patients is associated with incomplete extracellular matrix formation in a skin equivalent model. J Investig Dermatol 128(6):1442–1450PubMedCrossRefGoogle Scholar
  18. 18.
    Elahi E, Kalhor R, Banihosseini SS, Torabi N, Pour-Jafari H, Houshmand M, Amini SS, Ramezani A, Loeys B (2006) Homozygous missense mutation in fibulin-5 in an Iranian autosomal recessive cutis laxa pedigree and associated haplotype. J Invest Dermatol 126(7):1506–1509PubMedCrossRefGoogle Scholar
  19. 19.
    Hu Q, Loeys BL, Coucke PJ, De Paepe A, Mecham RP, Choi J, Davis EC, Urban Z (2006) Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive cutis laxa. Hum Mol Genet 15(23):3379–3386PubMedCrossRefGoogle Scholar
  20. 20.
    Hucthagowder V, Sausgruber N, Kim KH, Angle B, Marmorstein LY, Urban Z (2006) Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome. Am J Hum Genet 78(6):1075–1080PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Dasouki M, Markova D, Garola R, Sasaki T, Charbonneau NL, Sakai LY, Chu ML (2007) Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa. Am J Med Genet A 143A(22):2635–2641PubMedCrossRefGoogle Scholar
  22. 22.
    Hucthagowder V, Morava E, Kornak U, Lefeber DJ, Fischer B, Dimopoulou A, Aldinger A, Choi J, Davis EC, Abuelo DN, Adamowicz M, Al-Aama J, Basel-Vanagaite L, Fernandez B, Greally MT, Gillessen-Kaesbach G, Kayserili H, Lemyre E, Tekin M, Turkmen S, Tuysuz B, Yuksel-Konuk B, Mundlos S, Van Maldergem L, Wevers RA, Urban Z (2009) Loss-of-function mutations in ATP6V0A2 impair vesicular trafficking, tropoelastin secretion and cell survival. Hum Mol Genet 18(12):2149–2165PubMedCrossRefGoogle Scholar
  23. 23.
    Mégarbané H, Florence J, Sass JO, Schwonbeck S, Foglio M, de Cid R, Cure S, Saker S, Mégarbané A, Fischer J (2009) An autosomal-recessive form of cutis laxa is due to homozygous elastin mutations, and the phenotype may be modified by a heterozygous fibulin 5 polymorphism. J Invest Dermatol 129(7):1650–1655PubMedCrossRefGoogle Scholar
  24. 24.
    Berk DR, Bentley DD, Bayliss SJ, Lind A, Urban Z (2012) Cutis laxa: a review. J Am Acad Dermatol 66(5):842 e1–842 e17CrossRefGoogle Scholar
  25. 25.
    Morava E, Lefeber DJ, Urban Z, de Meirleir L, Meinecke P, Gillessen Kaesbach G, Sykut-Cegielska J, Adamowicz M, Salafsky I, Ranells J, Lemyre E, van Reeuwijk J, Brunner HG, Wevers RA (2008) Defining the phenotype in an autosomal recessive cutis laxa syndrome with a combined congenital defect of glycosylation. Eur J Hum Genet 16(1):28–35PubMedCrossRefGoogle Scholar
  26. 26.
    Kornak U, Reynders E, Dimopoulou A, van Reeuwijk J, Fischer B, Rajab A, Budde B, Nurnberg P, Foulquier F, A. D.-t. S. Group, Lefeber D, Urban Z, Gruenewald S, Annaert W, Brunner HG, van Bokhoven H, Wevers R, Morava E, Matthijs G, Van Maldergem L, Mundlos S (2008) Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+−ATPase subunit ATP6V0A2. Nat Genet 40(1):32–34PubMedCrossRefGoogle Scholar
  27. 27.
    Guillard M, Dimopoulou A, Fischer B, Morava E, Lefeber DJ, Kornak U, Wevers RA (2009) Vacuolar H+−ATPase meets glycosylation in patients with cutis laxa. Biochim Biophys Acta 1792(9):903–914PubMedCrossRefGoogle Scholar
  28. 28.
    Fischer B, Dimopoulou A, Egerer J, Gardeitchik T, Kidd A, Jost D, Kayserili H, Alanay Y, Tantcheva-Poor I, Mangold E, Daumer-Haas C, Phadke S, Peirano RI, Heusel J, Desphande C, Gupta N, Nanda A, Felix E, Berry-Kravis E, Kabra M, Wevers RA, van Maldergem L, Mundlos S, Morava E, Kornak U (2012) Further characterization of ATP6V0A2-related autosomal recessive cutis laxa. Hum Genet 131(11):1761–1773PubMedCrossRefGoogle Scholar
  29. 29.
    Van Maldergem L, Yuksel-Apak M, Kayserili H, Seemanova E, Giurgea S, Basel-Vanagaite L, Leao-Teles E, Vigneron J, Foulon M, Greally M, Jaeken J, Mundlos S, Dobyns WB (2008) Cobblestone-like brain dysgenesis and altered glycosylation in congenital cutis laxa, Debré-type. Neurology 71:1602–1608PubMedCrossRefGoogle Scholar
  30. 30.
    Morava E, Wevers RA, Willemsen MA, Lefeber D (2009) Cobblestone-like brain dysgenesis and altered glycosylation in congenital cutis laxa, Debre type. Neurology 73(14):1164; author reply 1164–1165Google Scholar
  31. 31.
    Morava E, Zeevaert R, Korsch E, Huijben K, Wopereis S, Matthijs G, Keymolen K, Lefeber DJ, De Meirleir L, Wevers RA (2007) A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia. Eur J Hum Genet 15(6):638–645PubMedCrossRefGoogle Scholar
  32. 32.
    Van Maldergem L, Vamos E, Liebaers I, Petit P, Vandevelde G, Simonis-Blumenfrucht A, Bouffioux R, Kulakowski S, Hanquinet S, Van Durme P et al (1988) Severe congenital cutis laxa with pulmonary emphysema: a family with three affected sibs. Am J Med Genet 31(2):455–464PubMedCrossRefGoogle Scholar
  33. 33.
    Mohamed M, Kouwenberg D, Gardeitchik T, Kornak U, Wevers RA, Morava E (2011) Metabolic cutis laxa syndromes. J Inherit Metab Dis 34(4):907–916PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Reversade B, Escande-Beillard N, Dimopoulou A, Fischer B, Chng SC, Li Y, Shboul M, Tham PY, Kayserili H, Al-Gazali L, Shahwan M, Brancati F, Lee H, O’Connor BD, Schmidt-von Kegler M, Merriman B, Nelson SF, Masri A, Alkazaleh F, Guerra D, Ferrari P, Nanda A, Rajab A, Markie D, Gray M, Nelson J, Grix A, Sommer A, Savarirayan R, Janecke AR, Steichen E, Sillence D, Hausser I, Budde B, Nurnberg G, Nurnberg P, Seemann P, Kunkel D, Zambruno G, Dallapiccola B, Schuelke M, Robertson S, Hamamy H, Wollnik B, Van Maldergem L, Mundlos S, Kornak U (2009) Mutations in PYCR1 cause cutis laxa with progeroid features. Nat Genet 41(9):1016–1021PubMedCrossRefGoogle Scholar
  35. 35.
    Guernsey DL, Jiang H, Evans SC, Ferguson M, Matsuoka M, Nightingale M, Rideout AL, Provost S, Bedard K, Orr A, Dube MP, Ludman M, Samuels ME (2009) Mutation in pyrroline-5-carboxylate reductase 1 gene in families with cutis laxa type 2. Am J Hum Genet 85(1):120–129PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Zampatti S, Castori M, Fischer B, Ferrari P, Garavelli L, Dionisi-Vici C, Agolini E, Wischmeijer A, Morava E, Novelli G, Haberle J, Kornak U, Brancati F (2012) De Barsy syndrome: a genetically heterogeneous autosomal recessive cutis laxa syndrome related to P5CS and PYCR1 dysfunction. Am J Med Genet A 158A(4):927–931PubMedCrossRefGoogle Scholar
  37. 37.
    Leao-Teles E, Quelhas D, Vilarinho L, Jaeken J (2010) De Barsy syndrome and ATP6V0A2-CDG. Eur J Hum Genet 18(5):526, author reply 526PubMedCrossRefGoogle Scholar
  38. 38.
    Kouwenberg D, Gardeitchik T, Wevers RA, Haberle J, Morava E (2011) Recognizable phenotype with common occurrence of microcephaly, psychomotor retardation, but no spontaneous bone fractures in autosomal recessive cutis laxa type IIB due to PYCR1 mutations. Am J Med Genet A 155A(9):2331–2332PubMedCrossRefGoogle Scholar
  39. 39.
    Martinelli D, Haberle J, Rubio V, Giunta C, Hausser I, Carrozzo R, Gougeard N, Marco-Marin C, Goffredo BM, Meschini MC, Bevivino E, Boenzi S, Colafati GS, Brancati F, Baumgartner MR, Dionisi-Vici C (2012) Understanding pyrroline-5-carboxylate synthetase deficiency: clinical, molecular, functional, and expression studies, structure-based analysis, and novel therapy with arginine. J Inherit Metab Dis 35(5):761–776PubMedCrossRefGoogle Scholar
  40. 40.
    Skidmore DL, Chitayat D, Morgan T, Hinek A, Fischer B, Dimopoulou A, Somers G, Halliday W, Blaser S, Diambomba Y, Lemire EG, Kornak U, Robertson SP (2011) Further expansion of the phenotypic spectrum associated with mutations in ALDH18A1, encoding Delta(1)-pyrroline-5-carboxylate synthase (P5CS). Am J Med Genet A 155A(8):1848–1856PubMedCrossRefGoogle Scholar
  41. 41.
    Noordam C, Funke S, Knoers NV, Jira P, Wevers RA, Urban Z, Morava E (2009) Decreased bone density and treatment in patients with autosomal recessive cutis laxa. Acta Paediatr 98(3):490–494PubMedCrossRefGoogle Scholar
  42. 42.
    Basel-Vanagaite L, Sarig O, Hershkovitz D, Fuchs-Telem D, Rapaport D, Gat A, Isman G, Shirazi I, Shohat M, Enk CD, Birk E, Kohlhase J, Matysiak-Scholze U, Maya I, Knopf C, Peffekoven A, Hennies HC, Bergman R, Horowitz M, Ishida-Yamamoto A, Sprecher E (2009) RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome. Am J Hum Genet 85(2):254–263PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Syx D, Malfait F, Van Laer L, Hellemans J, Hermanns-Le T, Willaert A, Benmansour A, De Paepe A, Verloes A (2010) The RIN2 syndrome: a new autosomal recessive connective tissue disorder caused by deficiency of Ras and Rab interactor 2 (RIN2). Hum Genet 128(1):79–88PubMedCrossRefGoogle Scholar
  44. 44.
    Albrecht B, de Brouwer AP, Lefeber DJ, Cremer K, Hausser I, Rossen N, Wortmann SB, Wevers RA, Kornak U, Morava E (2010) MACS syndrome: a combined collagen and elastin disorder due to abnormal Golgi trafficking. Am J Med Genet A 152A(11):2916–2918PubMedCrossRefGoogle Scholar
  45. 45.
    Valayannopoulos V, Verhoeven NM, Mention K, Salomons GS, Sommelet D, Gonzales M, Touati G, de Lonlay P, Jakobs C, Saudubray JM (2006) Transaldolase deficiency: a new cause of hydrops fetalis and neonatal multi-organ disease. J Pediatr 149(5):713–717PubMedCrossRefGoogle Scholar
  46. 46.
    Kleefstra T, Wortmann SB, Rodenburg RJ, Bongers EM, Hadzsiev K, Noordam C, van den Heuvel LP, Nillesen WM, Hollody K, Gillessen-Kaesbach G, Lammens M, Smeitink JA, van der Burgt I, Morava E (2011) Mitochondrial dysfunction and organic aciduria in five patients carrying mutations in the Ras-MAPK pathway. Eur J Hum Genet 19(2):138–144PubMedCrossRefGoogle Scholar
  47. 47.
    Callewaert B, Renard M, Hucthagowder V, Albrecht B, Hausser I, Blair E, Dias C, Albino A, Wachi H, Sato F, Mecham RP, Loeys B, Coucke PJ, De Paepe A, Urban Z (2011) New insights into the pathogenesis of autosomal-dominant cutis laxa with report of five ELN mutations. Hum Mutat 32(4):445–455PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Stone EM, Braun TA, Russell SR, Kuehn MH, Lotery AJ, Moore PA, Eastman CG, Casavant TL, Sheffield VC (2004) Missense variations in the fibulin 5 gene and age-related macular degeneration. N Engl J Med 351(4):346–353PubMedCrossRefGoogle Scholar
  49. 49.
    Auer-Grumbach M, Weger M, Fink-Puches R, Papic L, Frohlich E, Auer-Grumbach P, El Shabrawi-Caelen L, Ttl MS, Windpassinger C, Senderek J, Budka H, Trajanoski S, Janecke AR, Haas A, Metze D, Pieber TR, Guelly C (2011) Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin. Brain 134:1839–1852PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Jones RPO, Ridley C, Jowitt TA, Wang MC, Howard M, Bobola N, Wang T, Bishop PN, Kielty CM, Baldock C, Lotery AJ, Trump D (2010) Structural effects of fibulin 5 missense mutations associated with age-related macular degeneration and cutis laxa. Invest Ophthalmol Vis Sci 51(5):2356–2362PubMedCrossRefGoogle Scholar
  51. 51.
    Menkes JH, Alter M, Steigleder GK, Weakley DR, Sung JH (1962) A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. Pediatrics 29:764–779PubMedGoogle Scholar
  52. 52.
    Danks DM, Campbell PE, Walker-Smith J, Stevens BJ, Gillespie JM, Blomfield J, Turner B (1972) Menkes” kinky-hair syndrome. Lancet 1(7760):1100–1102PubMedCrossRefGoogle Scholar
  53. 53.
    Danks DM, Stevens BJ, Campkell PE, Cartwright EC, Gillespie JM, Townley RR, Blomfield J, Turner BB, Mayne V, Walker-Smith JA (1974) Menkes kinky-hair syndrome. An inherited defect in the intestinal absorption of copper with widespread effects. Birth Defects Orig Artic Ser 10(10):132–137PubMedGoogle Scholar
  54. 54.
    Yamaguchi Y, Heiny ME, Suzuki M, Gitlin JD (1996) Biochemical characterization and intracellular localization of the Menkes disease protein. Proc Natl Acad Sci U S A 93(24):14030–14035PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Camakaris J, Petris MJ, Bailey L, Shen PY, Lockhart P, Glover TW, Barcroft CL, Patton J, Mercer JFB (1995) Gene amplification of the Menkes (MNK, ATP7a) P-Type ATPase gene of CHO cells is associated with copper resistance and enhanced copper efflux. Hum Mol Genet 4(11):2117–2123PubMedCrossRefGoogle Scholar
  56. 56.
    Moller LB, Hicks JD, Holmes CS, Goldstein DS, Brendl C, Huppke P, Kaler SG (2011) Diagnosis of copper transport disorders. Curr Protoc Hum Genet Chapter 17: Unit 17.9Google Scholar
  57. 57.
    Haddad MR, Macri CJ, Holmes CS, Goldstein DS, Jacobson BE, Centeno JA, Popek EJ, Gahl WA, Kaler SG (2012) In utero copper treatment for Menkes disease associated with a severe ATP7A mutation. Mol Genet Metab 107(1–2):222–228PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Donsante A, Yi L, Zerfas PM, Brinster LR, Sullivan P, Goldstein DS, Prohaska J, Centeno JA, Rushing E, Kaler SG (2011) ATP7A gene addition to the choroid plexus results in long-term rescue of the lethal copper transport defect in a Menkes disease mouse model. Mol Ther 19(12):2114–2123PubMedCrossRefGoogle Scholar
  59. 59.
    Wopereis S, Lefeber DJ, Morava E, Wevers RA (2006) Mechanisms in protein O-glycan biosynthesis and clinical and molecular aspects of protein O-glycan biosynthesis defects: a review. Clin Chem 52(4):574–600PubMedCrossRefGoogle Scholar
  60. 60.
    Ng BG, Kranz C, Hagebeuk EE, Duran M, Abeling NG, Wuyts B, Ungar D, Lupashin V, Hartdorff CM, Poll-The BT, Freeze HH (2007) Molecular and clinical characterization of a Moroccan Cog7 deficient patient. Mol Genet Metab 91(2):201–204PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Spaapen LJ, Bakker JA, van der Meer SB, Sijstermans HJ, Steet RA, Wevers RA, Jaeken J (2005) Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder. J Inherit Metab Dis 28(5):707–714PubMedCrossRefGoogle Scholar
  62. 62.
    Wu X, Steet RA, Bohorov O, Bakker J, Newell J, Krieger M, Spaapen L, Kornfeld S, Freeze HH (2004) Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder. Nat Med 10(5):518–523PubMedCrossRefGoogle Scholar
  63. 63.
    Miller VJ, Ungar D (2012) Re‘COG’nition at the Golgi. Traffic 13(7):891–897PubMedCrossRefGoogle Scholar
  64. 64.
    Morava E, Wopereis S, Coucke P, Gillessen-Kaesbach G, Voit T, Smeitink J, Wevers R, Grunewald S (2005) Defective protein glycosylation in patients with cutis laxa syndrome. Eur J Hum Genet 13(4):414–421PubMedCrossRefGoogle Scholar
  65. 65.
    Kamoun P, Aral B, Saudubray JM (1998) A new inherited metabolic disease: delta1-pyrroline 5-carboxylate synthetase deficiency. Bull Acad Natl Med 182(1):131–137; discussion 138–139PubMedGoogle Scholar
  66. 66.
    Baumgartner MR, Hu CA, Almashanu S, Steel G, Obie C, Aral B, Rabier D, Kamoun P, Saudubray JM, Valle D (2000) Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. Hum Mol Genet 9(19):2853–2858PubMedCrossRefGoogle Scholar
  67. 67.
    Baumgartner MR, Rabier D, Nassogne MC, Dufier JL, Padovani JP, Kamoun P, Valle D, Saudubray JM (2005) Delta1-pyrroline-5-carboxylate synthase deficiency: neurodegeneration, cataracts and connective tissue manifestations combined with hyperammonaemia and reduced ornithine, citrulline, arginine and proline. Eur J Pediatr 164(1):31–36PubMedCrossRefGoogle Scholar
  68. 68.
    Smith RJ, Phang JM (1978) Proline metabolism in cartilage: the importance of proline biosynthesis. Metabolism 27(6):685–694PubMedCrossRefGoogle Scholar
  69. 69.
    Shafqat S, Velaz-Faircloth M, Henzi VA, Whitney KD, Yang-Feng TL, Seldin MF, Fremeau RT Jr (1995) Human brain-specific L-proline transporter: molecular cloning, functional expression, and chromosomal localization of the gene in human and mouse genomes. Mol Pharmacol 48(2):219–229PubMedGoogle Scholar
  70. 70.
    Phang JM, Pandhare J, Liu YM (2008) The metabolism of proline as microenvironmental stress substrate. J Nutr 138(10):2008s–2015sPubMedCentralPubMedGoogle Scholar
  71. 71.
    Bicknell LS, Pitt J, Aftimos S, Ramadas R, Maw MA, Robertson SP (2008) A missense mutation in ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), causes an autosomal recessive neurocutaneous syndrome. Eur J Hum Genet 16(10):1176–1186PubMedCrossRefGoogle Scholar
  72. 72.
    Adams E, Frank L (1980) Metabolism of proline and the hydroxyprolines. Annu Rev Biochem 49:1005–1061PubMedCrossRefGoogle Scholar
  73. 73.
    Saito K, Murai J, Kajiho H, Kontani K, Kurosu H, Katada T (2002) A novel binding protein composed of homophilic tetramer exhibits unique properties for the small GTPase Rab5. J Biol Chem 277(5):3412–3418PubMedCrossRefGoogle Scholar
  74. 74.
    Wopereis S, Grunewald S, Morava E, Penzien JM, Briones P, Garcia-Silva MT, Demacker PN, Huijben KM, Wevers RA (2003) Apolipoprotein C-III isofocusing in the diagnosis of genetic defects in O-glycan biosynthesis. Clin Chem 49(11):1839–1845PubMedCrossRefGoogle Scholar
  75. 75.
    Tall GG, Barbieri MA, Stahl PD, Horazdovsky BF (2001) Ras-activated endocytosis is mediated by the Rab5 guanine nucleotide exchange activity of RIN1. Dev Cell 1(1):73–82PubMedCrossRefGoogle Scholar
  76. 76.
    Bamatter F, Franceschetti A, Klein D, Sierro A (1950) Gerodermie osteodysplastique hereditaire. Ann Pediatr 174:126–127Google Scholar
  77. 77.
    Hennies HC, Kornak U, Zhang HK, Egerer J, Zhang X, Seifert W, Kuhnisch J, Budde B, Natebus M, Brancati F, Wilcox WR, Muller D, Kaplan PB, Rajab A, Zampino G, Fodale V, Dallapiccola B, Newman W, Metcalfe K, Clayton-Smith J, Tassabehji M, Steinmann B, Barr FA, Nurnberg P, Wieacker P, Mundlos S (2008) Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin. Nat Genet 40(12):1410–1412PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Grigoriev I, Splinter D, Keijzer N, Wulf PS, Demmers J, Ohtsuka T, Modesti M, Maly IV, Grosveld F, Hoogenraad CC, Akhmanova A (2007) Rab6 regulates transport and targeting of exocytotic carriers. Dev Cell 13(2):305–314PubMedCrossRefGoogle Scholar
  79. 79.
    Sun Y, Shestakova A, Hunt L, Sehgal S, Lupashin V, Storriw B (2007) Rab6 regulates both ZW10/RINT-1 and conserved oligomeric Golgi complex-dependent Golgi trafficking and homeostasis. Mol Biol Cell 8(10):4129–4142CrossRefGoogle Scholar
  80. 80.
    Verhoeven NM, Huck JHJ, Roos B, Struys EA, Salomons GS, Douwes AC, van der Knaap MS, Jakobs C (2001) Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway. Am J Hum Genet 68(5):1086–1092PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Engelke UFH, Zijlstra FSM, Mochel F, Valayannopoulos V, Rabier D, Kluijtmans LAJ, Perl A, Verhoeven-Duif NM, de Lonlay P, Wamelink MMC, Jakobs C, Morava E, Wevers RA (2010) Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency. Biochim Biophys Acta 1802(11):1028–1035PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Valayannopoulos V, Verhoeven NM, Mention K, Salomons GS, Sommelet D, Gonzales M, Touati G, De Lonlay P, Jakobs C, Saudubra JM (2006) Transaldolase deficiency: a new cause of hydrops fetalis and neonatal multi-organ disease. J Pediatr 149(5):713–717PubMedCrossRefGoogle Scholar
  83. 83.
    Gelb BD, Tartaglia M (2006) Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction. Hum Mol Genet 15:R220–R226PubMedCrossRefGoogle Scholar
  84. 84.
    Sarkozy A, Carta C, Moretti S, Zampino G, Digilio MC, Pantaleoni F, Scioletti AP, Esposito G, Cordeddu V, Lepri F, Petrangeli V, Dentici ML, Mancini GMS, Selicorni A, Rossi C, Mazzanti L, Marino B, Ferrero GB, Silengo MC, Memo L, Stanzial F, Faravelli F, Stuppia L, Puxeddu E, Gelb BD, Dallapiccola B, Tartaglia M (2009) Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. Hum Mutat 30(4):695–702PubMedCrossRefGoogle Scholar
  85. 85.
    Graul-Neumann LM, Hausser I, Essayie M, Rauch A, Kraus C (2008) Highly variable cutis laxa resulting from a dominant splicing mutation of the elastin gene. Am J Med Genet A 146A(8):977–983PubMedCrossRefGoogle Scholar
  86. 86.
    Borm B, Moller LB, Hausser I, Emeis M, Baerlocher K, Horn N, Rossi R (2004) Variable clinical expression of an identical mutation in the ATP7A gene for Menkes disease/occipital horn syndrome in three affected males in a single family. J Pediatr 145(1):119–121PubMedCrossRefGoogle Scholar
  87. 87.
    Mégarbané H, Florence J, Sass JO, Schwonbeck S, Foglio M, de Cid R, Cure S, Saker S, Mégarbané A, Fischer J (2009) An autosomal-recessive form of cutis laxa is due to homozygous elastin mutations, and the phenotype may be modified by a heterozygous fibulin 5 polymorphism. J Invest Dermatol 129(7):1650–1655PubMedCrossRefGoogle Scholar
  88. 88.
    Urban Z, Hucthagowder V, Schurmann N, Todorovic V, Zilberberg L, Choi J, Sens C, Brown CW, Clark RD, Holland KE, Marble M, Sakai LY, Dabovic B, Rifkin DB, Davis EC (2009) Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. Am J Hum Genet 85(5):593–605PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Guerra D, Fornieri C, Bacchelli B, Lugli L, Torelli P, Balli F, Ferrari P (2004) The De Barsy syndrome. J Cutan Pathol 31(9):616–624PubMedCrossRefGoogle Scholar
  90. 90.
    Kretz R, Bozorgmehr B, Kariminejad MH, Rohrbach M, Hausser I, Baumer A, Baumgartner M, Giunta C, Kariminejad A, Haberle J (2011) Defect in proline synthesis: pyrroline-5-carboxylate reductase 1 deficiency leads to a complex clinical phenotype with collagen and elastin abnormalities. J Inherit Metab Dis 34(3):731–739PubMedCrossRefGoogle Scholar
  91. 91.
    Nanda A, Alsaleh QA, Al-Sabah H, Marzouk EE, Salam AMA, Nanda M, Anim JT (2008) Gerodermia osteodysplastica/wrinkly skin syndrome: report of three patients and brief review of the literature. Pediatr Dermatol 25(1):66–71PubMedCrossRefGoogle Scholar
  92. 92.
    Boente MDC, Asial RA, Winik BC (2006) Geroderma osteodysplastica. Report of a new family. Pediatr Dermatol 23(5):467–472CrossRefGoogle Scholar
  93. 93.
    van Bon BWM, Gilissen C, Grange DK, Hennekam RCM, Kayserili H, Engels H, Reutter H, Ostergaard JR, Morava E, Tsiakas K, Isidor B, Le Merrer M, Eser M, Wieskamp N, de Vries P, Steehouwer M, Veltman JA, Robertson SP, Brunner HG, de Vries BBA, Hoischen A (2012) Cantu syndrome is caused by mutations in ABCC9. Am J Hum Genet 90(6):1094–1101PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Vanakker OM, Leroy BP, Schurgers LJ, Vermeer C, Coucke PJ, De Paepe A (2011) Atypical presentation of pseudoxanthoma elasticum with abdominal cutis laxa: evidence for a spectrum of ectopic calcification disorders? Am J Med Genet A 155A(11):2855–2859PubMedCrossRefGoogle Scholar
  95. 95.
    Vaccaro M, Salpietro DC, Briuglia S, Merlino MV, Guarneri F, Dallapiccola B (2005) Cutis laxa in Kabuki make-up syndrome. J Am Acad Dermatol 53(5 Suppl 1):S247–S251PubMedCrossRefGoogle Scholar
  96. 96.
    Nanda A, Anim JT, Al-Gareeb M, Alsaleh QA (2006) Keutel syndrome with overlapping features of cutis laxa: a new variant. Am J Med Genet A 140(13):1487–1489; author reply 1490PubMedCrossRefGoogle Scholar
  97. 97.
    Sayli BS, Gul D (1993) GAPO syndrome in three relatives in a Turkish kindred. Am J Med Genet 47(3):342–345PubMedCrossRefGoogle Scholar
  98. 98.
    Koppe R, Kaplan P, Hunter A, MacMurray B (1989) Ambiguous genitalia associated with skeletal abnormalities, cutis laxa, craniostenosis, psychomotor retardation, and facial abnormalities (SCARF syndrome). Am J Med Genet 34(3):305–312PubMedCrossRefGoogle Scholar
  99. 99.
    Haensel J, Kohlschmidt N, Pitz S, Keilmann A, Zenker M, Ullmann R, Haaf T, Bartsch O (2009) Case report supporting that the Barber-Say and ablepharon macrostomia syndromes could represent one disorder. Am J Med Genet A 149A(10):2236–2240PubMedCrossRefGoogle Scholar
  100. 100.
    d’Erme AM, Gola MF, Paradisi M, Passarelli F, Milanesi N, Gola M (2012) Skin signs as early manifestations of Hutchinson-Gilford progeria syndrome. Arch Dis Child 97(9):806–807PubMedCrossRefGoogle Scholar
  101. 101.
    Arboleda G, Morales LC, Quintero L, Arboleda H (2011) Neonatal progeroid syndrome (Wiedemann-Rautenstrauch syndrome): report of three affected sibs. Am J Med Genet A 155A(7):1712–1715PubMedCrossRefGoogle Scholar
  102. 102.
    Callewaert B, Su CT, Van Damme T, Vlummens P, Malfait F, Vanakker O, Schulz B, Mac Neal M, Davis EC, Lee JG, Salhi A, Unger S, Heimdal K, De Almeida S, Kornak U, Gaspar H, Bresson JL, Prescott K, Gosendi ME, Mansour S, Pierard GE, Madan-Khetarpal S, Sciurba FC, Symoens S, Coucke PJ, Van Maldergem L, Urban Z, De Paepe A (2013) Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa. Hum Mutat 34(1):111–121PubMedCrossRefGoogle Scholar
  103. 103.
    Yildirim Y, Tolun A, Tuysuz B (2011) The phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than autosomal recessive cutis laxa type 2. Am J Med Genet A 155A(1):134–140PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Miski Mohamed
    • 1
    Email author
  • Michiel Voet
    • 1
  • Thatjana Gardeitchik
    • 1
  • Eva Morava
    • 1
    • 2
  1. 1.Radboud University Nijmegen Medical Center, IGMDNijmegenThe Netherlands
  2. 2.Tulane University Medical Health Center, Hayward Genetics CenterNew OrleansUSA

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