TY - JOUR T1 - First evidence of a paediatric patient with Cornelia de Lange syndrome with acute lymphoblastic leukaemia JF - Journal of Clinical Pathology JO - J Clin Pathol SP - 558 LP - 561 DO - 10.1136/jclinpath-2019-205707 VL - 72 IS - 8 AU - Grazia Fazio AU - Valentina Massa AU - Andrea Grioni AU - Vojtech Bystry AU - Silvia Rigamonti AU - Claudia Saitta AU - Marta Galbiati AU - Carmelo Rizzari AU - Caterina Consarino AU - Andrea Biondi AU - Angelo Selicorni AU - Giovanni Cazzaniga Y1 - 2019/08/01 UR - http://jcp.bmj.com/content/72/8/558.abstract N2 - Cornelia de Lange syndrome (CdLS) is a rare autosomal-dominant genetic disorder characterised by prenatal and postnatal growth and mental retardation, facial dysmorphism and upper limb abnormalities. Germline mutations of cohesin complex genes SMC1A, SMC3, RAD21 or their regulators NIPBL and HDAC8 have been identified in CdLS as well as somatic mutations in myeloid disorders. We describe the first case of a paediatric patient with CdLS with B-cell precursor Acute Lymphoblastic Leukaemia (ALL). The patient did not show any unusual cytogenetic abnormality, and he was enrolled into the high risk arm of AIEOP-BFM ALL2009 protocol because of slow early response, but 3 years after discontinuation, he experienced an ALL relapse. We identified a heterozygous mutation in exon 46 of NIPBL, causing frameshift and a premature stop codon (RNA-Targeted Next generation Sequencing Analysis). The analysis of the family indicated a de novo origin of this previously not reported deleterious variant. As for somatic cohesin mutations in acute myeloid leukaemia, also this ALL case was not affected by aneuploidy, thus suggesting a major impact of the non-canonical role of NIPBL in gene regulation. A potential biological role of NIPBL in leukaemia has still to be dissected. ER -