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 a 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, roč. 72, č. 8, s. 558-561. ISSN 0021-9746. Dostupné z: https://dx.doi.org/10.1136/jclinpath-2019-205707.

Základní údaje

• Originální název: First evidence of a paediatric patient with Cornelia de Lange syndrome with acute lymphoblastic leukaemia
• Autoři: FAZIO, G., V. MASSA, Andrea GRIONI (380 Itálie, domácí), Vojtěch BYSTRÝ (203 Česká republika, garant, domácí), S. RIGAMONTI, C. SAITTA, M. GALBIATI, C. RIZZARI, C. CONSARINO, A. BIONDI, A. SELICORNI a G. CAZZANIGA.
• Vydání: Journal of clinical pathology, London, BMJ Publishing Group, 2019, 0021-9746.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 30109 Pathology
• Stát vydavatele: Velká Británie a Severní Irsko
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 2.460
• Kód RIV: RIV/00216224:14740/19:00113418
• Organizační jednotka: Středoevropský technologický institut
• Doi: http://dx.doi.org/10.1136/jclinpath-2019-205707
• UT WoS: 000478888000009
• Klíčová slova anglicky: molecular genetics; haemato-oncology; molecular oncology; paediatric haematology; paediatric pathology
• Štítky: rivok
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

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.