Eamonn Sheridan

Radiographs of limbs in WNT7A phocomelia 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).

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

Downey LM, Bottomley HM, Sheridan E, Ahmed M, Gilmour DF, Inglehearn CF, Reddy A, Agrawal A, Bradbury J, Toomes C (2006) Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5. Br J Ophthalmol 90:1163-7.

Thomas AC, Cullup T, Norgett EE, Hill T, Barton S, Dale BA, Sprecher E, Sheridan E, Taylor AE, Wilroy RS, Delozier C, Burrows N, Goodyear H, Fleckman P, Stephens KG, Mehta L, Watson RM, Graham R, Wolf R, Slavotinek A, Martin M, Bourn D, Mein CA, O'toole EA, Kelsell DP (2006) ABCA12 Is the Major Harlequin Ichthyosis Gene. J Invest Dermatol 126:2408-13.

Richardson RJ, Joss S, Tomkin S, Ahmed M, Sheridan E, Dixon MJ (2006) A nonsense mutation in the first transmembrane domain of connexin 43 underlies autosomal recessive oculodentodigital syndrome. J Med Genet 43:e37.