PMC6852097_01
Photograph of the forearm of the proband II2 and mother I2. (A). Photograph of the forearm of the proband II2 showing a Madelung deformity and bowing of the radius (blue and red arrows). This photograph shows the curve and shortening of the forearm, hand and wrist, the structure of which appears like that of a dinner fork. (B). Photograph of the forearm of the mother I2 showing a normal phenotype.
fgene-10-01086-g001.jpg
PMC6852097_01_fgene-10-01086-g001.jpg
f1
The proband II2 is a 35-year-old Chinese woman with a short stature (150 cm, -1.1SD), bilateral Madelung deformity, bowing of the radius, and mesomelia affecting the arms, in particular, which was a typical LWD phenotype ( Figure 1A ). It was observed that the mother was healthy with a height of 163cm (+1.1SD) and completely normal arms ( Figure 1B ).
Characteristics of the 5,707 kb and 857 kb deletions of Xq25q26.3 and Xp22.33, respectively. (A). Results of cfDNA screening of the pregnant proband. cfDNA screening study of the maternal plasma, illustrating an uncertain 6 Mb deletion in the long arm of the X-chromosome (128M-133M), Z score = -19.43. (B and C). SNP array analysis of the fetus (III1) and the couples (II1, II2). (B). The red bar indicates a heterozygous 5,707 kb deletion in Xq25q26.3 (chrX: 127,915,006-133,621,667) in the fetus (III1). (C). The red bar indicates a heterozygous 857 kb deletion in Xp22.33 (chrX: 784,064-1,640,746) in the fetus (III1) and the pregnant proband (II2). (D). Pseudoautosomal region (PAR1) of the X and Y chromosomes. The 857 kb deletion in Xp22.33 (red bar) was located 164 kb downstream of the SHOX gene (chrX: 585,079-620,146), including the evolutionarily conserved CNE9 (blue bar), which was the SHOX gene enhancer. (E). For the proband II2, FISH experiment showed that the Xp22.3 deletion (detected by the probe RP11-1119O18, Spectrum Green) and the Xq25q26 deletion (detected by the probe RP11-313D19, Spectrum Red) located on the different X chromosomes, respectively.
fgene-10-01086-g002.jpg
PMC6852097_01_fgene-10-01086-g002.jpg
f2
Triple tests on chromosomes 13, 18, and 21 showed a low risk in NIPT; however, a 6 Mb deletion in the long arm of the X-chromosome (Z-score was -19.43) was detected, which was anticipated to have a maternal origin ( Figure 2A ).