RT Journal Article SR Electronic T1 Intragenic KANSL1 mutations and chromosome 17q21.31 deletions: broadening the clinical spectrum and genotype–phenotype correlations in a large cohort of patients JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 804 OP 814 DO 10.1136/jmedgenet-2015-103184 VO 52 IS 12 A1 Marcella Zollino A1 Giuseppe Marangi A1 Emanuela Ponzi A1 Daniela Orteschi A1 Stefania Ricciardi A1 Serena Lattante A1 Marina Murdolo A1 Domenica Battaglia A1 Ilaria Contaldo A1 Eugenio Mercuri A1 Maria Chiara Stefanini A1 Roseline Caumes A1 Patrick Edery A1 Massimiliano Rossi A1 Maria Piccione A1 Giovanni Corsello A1 Matteo Della Monica A1 Francesca Scarano A1 Manuela Priolo A1 Mattia Gentile A1 Giuseppe Zampino A1 Raymon Vijzelaar A1 Omar Abdulrahman A1 Anita Rauch A1 Beatrice Oneda A1 Matthew A Deardorff A1 Sulagna C Saitta A1 Marni J Falk A1 Holly Dubbs A1 Elaine Zackai YR 2015 UL http://jmg.bmj.com/content/52/12/804.abstract AB Background The 17q21.31 deletion syndrome phenotype can be caused by either chromosome deletions or point mutations in the KANSL1 gene. To date, about 60 subjects with chromosome deletion and 4 subjects with point mutation in KANSL1 have been reported. Prevalence of chromosome deletions compared with point mutations, genotype–phenotype correlations and phenotypic variability have yet to be fully clarified.Methods We report genotype–phenotype correlations in 27 novel subjects with 17q21.31 deletion and in 5 subjects with KANSL1 point mutation, 3 of whom were not previously reported.Results The prevalence of chromosome deletion and KANSL1 mutation was 83% and 17%, respectively. All patients had similar clinical features, with the exception of macrocephaly, which was detected in 24% of patients with the deletion and 60% of those with the point mutation, and congenital heart disease, which was limited to 35% of patients with the deletion. A remarkable phenotypic variability was observed in both categories, mainly with respect to the severity of ID. Cognitive function was within normal parameters in one patient in each group. Craniosynostosis, subependymal heterotopia and optic nerve hypoplasia represent new component manifestations.Conclusions In KANSL1 haploinsufficiency syndrome, chromosome deletions are greatly prevalent compared with KANSL1 mutations. The latter are sufficient in causing the full clinical phenotype. The degree of intellectual disability (ID) appears to be milder than expected in a considerable number of subjects with either chromosome deletion or KANSL1 mutation. Striking clinical criteria for enrolling patients into KANSL1 analysis include speech delay, distinctive facial dysmorphism, macrocephaly and friendly behaviour.