Advertisement

A case of TUBA1A mutation presenting with lissencephaly and Hirschsprung disease

      Abstract

      Gene mutation of tubulin alpha-1A (TUBA1A), a critical component of microtubules of the cytoskeleton, impairs neural migration and causes lissencephaly (LIS). The approximately 45 cases of disease-associated TUBA1A mutations reported to date demonstrate a wide spectrum of phenotypes. Here we describe an 8-year-old girl with lissencephaly, microcephaly, and early-onset epileptic seizures associated with a novel mutation in the TUBA1A gene. The patient developed Hirschsprung disease and the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which had not previously been described in TUBA1A mutation-associated disease. Our case provides new insight into the wide spectrum of disease phenotypes associated with TUBA1A mutation.

      Keywords

      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:

      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Coksaygan T.
        • Magnus T.
        • Cai J.
        • Mughal M.
        • Lepore A.
        • Xue H.
        • et al.
        Neurogenesis in Tα-1 tubulin transgenic mice during development and after injury.
        Exp Neurol. 2006; 197: 475-485
        • Keays D.A.
        • Tian G.
        • Poirier K.
        • Huang G.J.
        • Siebold C.
        • Cleak J.
        • et al.
        Mutations in α-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans.
        Cell. 2007; 128: 45-57
        • Morris-Rosendahl D.J.
        • Najm J.
        • Lachmeijer A.M.A.
        • Sztriha L.
        • Martins M.
        • Kuechler A.
        • et al.
        Refining the phenotype of α-1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly.
        Clin Genet. 2008; 74: 425-433
        • Sohal A.P.S.
        • Montgomery T.
        • Mitra D.
        • Ramesh V.
        TUBA1A mutation-associated lissencephaly: case report and review of the literature.
        Pediatr Neurol. 2012; 46: 127-131
        • Kumar R.A.
        • Pilz D.T.
        • Babatz T.D.
        • Cushion T.D.
        • Harvey K.
        • Topf M.
        • et al.
        TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins.
        Hum Mol Genet. 2010; 19: 2817-2827
      1. Poirier K, Saillour Y, Fourniol F, Francis F, Souville I, Valence S, et al. Expanding the spectrum of TUBA1A-related cortical dysgenesis to polymicrogyria. Eur J Hum Genet, in press. http://dx.doi.org/10.1038/ejhg.2012.195.

        • Tanteles G.A.
        • Kurup B.
        • Rauch A.
        • Splitt M.P.
        Microcephaly, lissencephaly, Hirschsprung disease, and tetralogy of Fallot: a new syndrome?.
        Clin Dysmorphol. 2006; 15: 107-110
        • Amiel J.
        • Lyonnet S.
        Hirschsprung disease, associated syndromes, and genetics: a review.
        J Med Genet. 2001; 38: 729-739
        • Francis R.
        • Xu X.
        • Park H.
        • Wei C.J.
        • Chang S.
        • Chatterjee B.
        • et al.
        Connexin43 modulates cell polarity and directional cell migration by regulating microtubule dynamics.
        PLoS One. 2011; 6: e26379
        • Lo C.W.
        • Waldo K.L.
        • Kirby M.L.
        Gap junction communication and the modulation of cardiac neural crest cells.
        Trends Cardiovasc Med. 1999; 9: 63-69
        • Clauss S.B.
        • Walker D.L.
        • Kirby M.L.
        • Schimel D.
        • Lo C.W.
        Patterning of coronary arteries in wildtype and connexin43 knockout mice.
        Dev Dyn. 2006; 235: 2786-2794
        • Nemeth L.
        • Maddur S.
        • Puri P.
        Immunolocalization of the gap junction protein connexin 43 in the interstitial cells of cajal in the normal and Hirschsprung’s disease bowel.
        J Pediatr Surg. 2000; 35: 823-828
        • Thomas T.
        • Jordan K.
        • Simek J.
        • Shao Q.
        • Jedeszko C.
        • Walton P.
        • et al.
        Mechanisms of Cx43 and Cx26 transport to the plasma membrane and gap junction regeneration.
        J Cell Sci. 2005; 118: 4451-4462
        • Giepmans B.N.G.
        • Verlaan I.
        • Moolenaar W.H.
        Connexin-43 interactions with ZO-1 and α- and β-tubulin.
        Cell Commun Adhes. 2001; 8: 219-223
        • Amini A.
        • Schmidt M.H.
        Syndrome of inappropriate secretion of antidiuretic hormone and hyponatremia after spinal surgery.
        Neurosurg Focus. 2004; 16: E10