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Short report
Biallelic variants in BRCA1 gene cause a recognisable phenotype within chromosomal instability syndromes reframed as BRCA1 deficiency
  1. Adela Chirita-Emandi1,2,
  2. Nicoleta Andreescu1,2,
  3. Cristina Popa1,
  4. Alexandra Mihailescu1,
  5. Anca-Lelia Riza3,4,
  6. Razvan Plesea3,4,
  7. Mihai Ioana3,4,
  8. Smaranda Arghirescu5,6,
  9. Maria Puiu1,2
  1. 1Department of Microscopic Morphology - Genetics, Center of Genomic Medicine, Victor Babes University of Medicine and Pharmacy Timisoara, Timisoara, Romania
  2. 2Regional Center of Medical Genetics Timis, Genetics, Emergency Hospital for Children Louis Turcanu Timisoara, Timisoara, Romania
  3. 3Human Genomics Laboratory, Genetics, University of Medicine and Pharmacy of Craiova, Craiova, Romania
  4. 4Regional Center of Medical Genetics Dolj, Emergency Clinical County Hospital Craiova, Craiova, Romania
  5. 5Pediatric Department – Pediatric Discipline III, Victor Babes University of Medicine and Pharmacy Timisoara, Timisoara, Timis, Romania
  6. 6Onco-Hematology Department, Emergency Hospital for Children Louis Turcanu Timisoara, Timisoara, Timis, Romania
  1. Correspondence to Dr Adela Chirita-Emandi, Genetics, Universitatea de Medicina si Farmacie Victor Babes din Timisoara, Timisoara 300041, Romania; adela.chirita{at}


Pathogenic variants in BRCA1 gene in heterozygous state are known to be associated with breast-ovarian cancer susceptibility; however, biallelic variants cause a phenotype recognised as Fanconi anaemia complementation group S. Due to its rarity, medical management and preventive screening measures are insufficiently understood. Here, we present nine individuals (one new and eight previously presented) with biallelic variants in BRCA1 gene, to delineate clinical features in comparison with other chromosome instability syndromes and understand the patients’ health risk. Features seen in these 9 individuals (7 females/2 males) include prenatal and postnatal growth failure (9/9), microcephaly (9/9), hypo/hyperpigmented lesions (9/9), facial dysmorphism (9/9), mild developmental delay (8/9) and early-onset solid tumours (5/9). None presented bone marrow failure or immunodeficiency. Individuals with biallelic variants in BRCA1 also showed chromosomal instability by mitomycin and diepoxybutane test. The phenotype caused by biallelic BRCA1 variants is best framed between Fanconi anaemia and Nijmegen syndrome, yet distinct due to lack of bone marrow failure and immunodeficiency. We hypothesise that disease class should be reframed and medical management in people with biallelic variants in BRCA1 should emphasise on detection of solid tumour development and avoiding exposure to ionising radiation.

  • genetics
  • child health
  • diagnosis

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  • Contributors AC-E collected patient’s data and summarised clinical and genetic findings. AC-E, NA, CP, AM, A-LR, RP and MI participated in genetic studies, genetic analyses, bioinformatics and data interpretation. AC-E, SA and MP followed the patient. AC-E drafted the manuscript. All coauthors critically reviewed the manuscript and approved the final submitted version.

  • Funding The research was performed in the Center of Genomic Medicine University of Medicine and Pharmacy ‘Victor Babes’ POSCCE project ID:1854, SMIS code 48749, contract 677/09.04.2015.

  • Competing interests None declared.

  • Patient consent for publication Parental/guardian consent obtained.

  • Ethics approval This study was approved by the University of Medicine and Pharmacy ‘Victor Babes’ Timisoara Ethics Committee (no. 9/30.04.2020).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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