Fig. 1.

Structure of the TANGO1 gene and protein, clinical findings of the Indian consanguineous family, and overview of the exome filter strategy. (A) The TANGO1 gene consists of 28 exons (8142 bp) and comprises 49.91 kb on chromosome 1. Full‐length TANGO1 protein consists of 1907 amino acids, and contains luminal, transmembrane, and cytosolic domains. TANGO1‐short lacks the luminal portion and contains the domains shown in color gradient. The earlier identified pathogenic variant p.(Arg1207=) and our variant p.(Leu924Serfs*) are highlighted. (B) Pedigree of the Indian family with reported consanguinity. The proband (IV:4) is indicated with an arrow, asterisks denote family members available for molecular testing, the parents are obligate carriers of the identified variant. (C) Anterior–posterior radiographs from IV:4 at 13 weeks of gestation reveal short and bowed extremities and a remarkable undermineralization throughout the whole body. (D) WES generated 32332 variants in the proband that differed from the consensus genomic sequence (GRCh37/hg19), and ExomeDepth called 229 rare CNVs (93 duplications and 136 deletions). No variant or CNV was retained when filtering the whole exome dataset for the known OI genes (left), 6 candidates resulted from retaining variants that correspond to the combination of 6 filter settings (right).