Fig. 1

a The index case presented with intrauterine growth retardation, microcephaly, dysmorphism, with clinical suspicion of a lysosomal disease. GS detected a heterozygous intronic deletion (NM_024312.4(GNPTAB):c.2915+4_2915+9del, inherited from the father) and a maternally inherited heterozygous insertion within exon 13 of the GNPTAB gene (mucolipidosis type II). Corresponding IGV images are shown with the small intronic deletion (left) and large exonic insertion (right). The exonic insertion was confirmed by PCR and gel electrophoresis, index and mother presented a larger band corresponding to the allele with the insertion. b The index patient presented with neurodevelopmental delay, microcephaly, abnormal skin pigmentation, reticular rash and photophobia. GS identified a heterozygous missense variant (NM_000057.2(BLM):c.3164G>C, p.(Cys1055Ser), Sanger traces are shown) and a heterozygous deletion encompassing exons 11 and 12 of the BLM gene (indicated by red arrows, IGV). Note comparation in IGV of ES and GS data (only index, upper lane) in the corresponding region of the BLM gene. c The index patient presented with neurodevelopmental delay, short stature, facial dysmorphism (hypertelorism, low set ears) and cardiovascular malformation (coarctation of the aorta and persistent ductus arteriosus). A structural variant was detected by GS: a balanced translocation between chromosomes 1p (left panel) and 3p (right panel) with break points definitions at chr1:3,300,737 and chr3:51,573,020. The break points are likely affecting the PRDM16 and RAD54L2 genes which have been implicated in cardiomyopathy and neurodevelopmental delay. Upper panel: Additional confirmation was performed, by agarose gel electrophoresis (1.5%) of PCR amplified products of control fragment and translocation testing fragment. Control fragment shows amplification corresponding to size 403 bp for two controls samples (CTRL_1, CTRL_2) and patient. Translocation testing fragment shows amplification corresponding to size 803 bp only for patient sample. d Index case presented with failure to thrive, fatigue, metabolic acidosis, polyuria, polydipsia. GS did not detect any abnormality in the nuclear DNA. A large heteroplasmic deletion was detected in the mitochondrial DNA (chrM:8637–16072, indicated by red arrows) confirming the diagnosis of mitochondrial deletion syndrome.