Eamonn Sheridan
We have recently studied a new phocomelia syndrome, characterised by pleiotropic abnormalities of the skeleton of the upper and lower limbs (see Figure). Autozygosity mapping revealed a minimal region on chromosome 3p25. This allowed identification of WNT7A mutations in two families, and further work on this gene continues in other families.
Other genes identified through similar approaches include one responsible for recessive ichthyosis (harlequin syndrome). We are also currently studying another novel phenotype, seen in local families with structural brain abnormalities and optic atrophy, as well as more familiar conditions such as primary ciliary dyskinesia (PCD) and cerebral palsy (CP).
Abdollahi MR, Morrison E, Sirey T, Molnar Z, Hayward BE, Carr IM, Springell K, Woods CG, Ahmed M, Hattingh L, Corry P, Pilz DT, Stoodley N, Crow Y, Taylor GR, Bonthron DT, Sheridan E (2009) Mutation of the variant alpha-tubulin TUBA8 results in polymicrogyria with optic nerve hypoplasia. Am J Hum Genet 85:737-44.
Bockenhauer D, Feather S, Stanescu HC, Bandulik S, Zdebik AA, Reichold M, Tobin J, Lieberer E, Sterner C, Landoure G, Arora R, Sirimanna T, Thompson D, Cross JH, van’t Hoff W, Al Masri O, Tullus K, Yeung S, Anikster Y, Klootwijk E, Hubank M, Dillon MJ, Heitzmann D, Arcos-Burgos M, Knepper MA, Dobbie A, Gahl WA, Warth R, Sheridan E, Kleta R (2009) Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N Engl J Med 360:1960-70.
De Vos M, Hayward BE, Charlton R, Taylor GR, Glaser AW, Picton S, Cole TR, Maher ER, McKeown CM, Mann JR, Yates JR, Baralle D, Rankin J, Bonthron DT, Sheridan E (2006) PMS2 mutations in childhood cancer. J Natl Cancer Inst 98:358-61.
Woods CG, Stricker S, Seemann P, Stern R, Cox J, Sheridan E, Roberts E,
Springell K, Scott S, Karbani G, Sharif SM, Toomes C, Bond J, Kumar D, Al-Gazali
L, Mundlos S (2006) Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome. Am J Hum Genet 79:402-8
Last modified: 13 May 2010