Fig. 1: Overlapping deletion in seven families presenting a new cardiac entity associating electrical disorder and developmental defects recapitulated in a mouse model.

a Pedigree of seven families presenting a new cardiac entity. Symbols marked by a slash indicate that the subject was deceased. Males were indicated by squares and females by circles. Black symbols represent individuals who present at least one of the cardiac phenotypes listed in Table 1 according to clinical examination. “+” symbol denotes deletion carriers and “−” symbol non-carrier. The proband is indicated by the arrow. b Overview of the 4q25 human locus in UCSC Genome browser with the reference genome assembly hg19. Genes are represented in black and blue. 7 Deletions sizes are represented in different horizontal color lines: red/Family#1 (chr4:112555060-112570371), green/Family#2, brown/Family#3, yellow/Family#4, Blue/Family#5, dark blue/Family#6 and purple/Family#7. Human-mouse conservation is measured by Cons 46-way (phastCons and phyloP score) provided by UCSC Genome browser. c Graphs depict individual and average measurements for RR interval and cumulative number of patients presenting sinus node dysfunction (SND), atrial fibrillation (AF), atrial septal defect (ASD) in deletion carriers (RR interval n = 70, SND n = 69, AF n = 58, ASD n = 58) and non-carriers (RR interval n = 31, SND n = 33, AF n = 32, ASD n = 27) in the seven families. Significance for each parameter was determined with two-sided Mann–Whitney test (RR interval p < 1.0E−04) and two-sided Fisher’s exact test (SND p < 2.2E−16, AF p = 2.1E−05, ASD p = 3.7E−03). d Representation of the reverse orthologous mouse locus in UCSC Genome browser with the reference genome assembly mm10. Genes are represented in black and blue. Homozygous 15Kb deletion generated in the mouse model is represented in red delimited by the dashed black lines. e Graphs show individual and average RR interval, Standard deviation of NN intervals (SDNN; heart rate variation), the duration of atrial arrhythmia (AA) episode (WT, n = 25, DelB, n = 15) after two pacing passes, number of mice with at least one episode lasting >1 s is indicated above each bar graph of control (n = 25) and DelB (n = 15) mice. Number of mice from control (n = 10) and DelB (n = 12) presenting atrial septal defect are depicted above bar graph. Significance for each parameter was determined with two-sided Welch’s t test (RR p = 0.0002), two-sided Mann–Whitney test (SDNN p = 6.3E−05, AA duration p = 1.18E−5), or two-sided Fisher’s exact test (AA inducibility p = 0.0021, ASD Adult p = 0.0396). Individual data are available in Supplementary Data 1 and in the Source Data file.