(A) Clinical photographs of the fetus at 21 weeks and 5 days, presenting with hydrops, shortened extremities, protruding abdomen, and short trunk. (B) Radiographs in frontal and lateral view show delayed ossification of spine and pelvis. Note the barrel-shaped thorax with horizontally oriented ribs and the extremely shortened long bones. (C) Sanger sequencing of genomic DNA demonstrates a homozygous mutation of the LBR gene (c.[366+1g>t];[366+1g>t]) that abrogates the splice donor site of exon 3. The abridged pedigree above shows cosegregation of the LBR mutation; *termination of pregnancy (TOP) because of cardiac malformation. (D) Exon-spanning reverse transcription PCR analysis of LBR (35 cycles) using cDNA derived from patient and matched control fibroblasts (CTL1, 2). Below: Schematic representation and electropherogram of the amplified/sequenced region and the splice mutation of LBR (indicated by a red arrow) that causes a partial deletion of exon 3, leading to a frameshift and premature termination codon in the open reading frame of LBR (p.E112Sfs*39). Gray horizontal arrows indicate the relative position of primers (not to scale).