Research Subjects
Genomic DNA from the affected individuals and family members was extracted from peripheral blood by standard methods or obtained from saliva samples with Oragene collection kits according to the manufacturer’s instructions. Informed consent was obtained from all participating families, and all procedures performed in studies involving human participants were in accordance with the Declaration of Helsinki. Research studies were approved by the Scottish Multicenter Research Ethics Committee (05/MRE00/74), the Hospital Universitario La Paz Ethical Committee (PI-2630), the Great Ormond Street Hospital Research Ethics Committee (09/H0706/66), the University Medical Center Göttingen Ethics Committee (vote ref. 3/2/1), and the Institute for Genomic Medicine at Columbia University (protocol AAAO8410).
Parents provided written consent for the publication of photographs of the affected individuals. For growth measurements, Z scores (standard deviations from population mean for age and sex) were calculated according to LMS (L, smooth curve; M, median; S, coefficient of variation) growth on the basis of British 1990 growth reference data.20 For calculation of Z scores for growth measurements published for Bloom syndrome,21 full-term gestation was assumed, and postnatal growth measurements were calculated from data provided for the 18- to 21-year age range.