Fig. 1: Identification of two families segregating recessive INTS13 variants.

a Pedigree of Family 1 (top): affected individuals (II.4 and II.5) were born to first-cousin parents (I.1 and I.2) with three unaffected children (II.1-II.3). Double lines indicate a consanguineous marriage. Pedigree of Family 2 (bottom): affected individuals (II.2 and II.4) were born to parents with two unaffected children (II.1 and II.3). b Homozygosity mapping of Family 1 delineated five candidate loci totaling 46 cM on chromosomes 6, 8, 12, 13, and 16. c Schematic representation of human INTS13 located on chromosome 12 (ch12p13.2-p11.22) consisting of 17 exons. Locus capture followed by massive parallel sequencing identified a homozygous frameshift mutation as a disease-causing mutation in Family 1. The c.2004delA (p.K668Nfs*9) mutation is caused by a single base pair deletion in exon 16 (marked in brown), resulting in a frameshift and premature termination codon (PTC) which alters nine amino acids (marked in red) and deletes the last 31. In Family 2, the c.1955C > T (p.S652L) mutation is caused by a single base pair substitution in exon 16 (marked in green). d Amino acid alignment of the C-terminus of the INTS13 protein shows that both mutations occur at highly conserved residues. Red and yellow shading indicates regions of conservation. Source data are provided as a Source Data file.