First evidence of a paediatric patient with Cornelia de Lange syndrome with acute lymphoblastic leukaemia

FAZIO, G., V. MASSA, Andrea GRIONI, Vojtěch BYSTRÝ, S. RIGAMONTI, C. SAITTA, M. GALBIATI, C. RIZZARI, C. CONSARINO, A. BIONDI, A. SELICORNI and G. CAZZANIGA. First evidence of a paediatric patient with Cornelia de Lange syndrome with acute lymphoblastic leukaemia. Journal of clinical pathology. London: BMJ Publishing Group, 2019, vol. 72, No 8, p. 558-561. ISSN 0021-9746. Available from: https://dx.doi.org/10.1136/jclinpath-2019-205707.

Basic information

• Original name: First evidence of a paediatric patient with Cornelia de Lange syndrome with acute lymphoblastic leukaemia
• Authors: FAZIO, G., V. MASSA, Andrea GRIONI (380 Italy, belonging to the institution), Vojtěch BYSTRÝ (203 Czech Republic, guarantor, belonging to the institution), S. RIGAMONTI, C. SAITTA, M. GALBIATI, C. RIZZARI, C. CONSARINO, A. BIONDI, A. SELICORNI and G. CAZZANIGA.
• Edition: Journal of clinical pathology, London, BMJ Publishing Group, 2019, 0021-9746.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30109 Pathology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 2.460
• RIV identification code: RIV/00216224:14740/19:00113418
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1136/jclinpath-2019-205707
• UT WoS: 000478888000009
• Keywords in English: molecular genetics; haemato-oncology; molecular oncology; paediatric haematology; paediatric pathology
• Tags: rivok
• Tags: International impact, Reviewed

Abstract

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.