Molecular cytogenetic characterization and prenatal diagnosis of familial Xp22.33 microdeletion encompassing short stature homeobox gene in a male fetus with a favorable outcome

摘要

A 34-year-old, gravida 1, para 0, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. She had a body height of 150 cm. Her husband was 38 years old and had a body height of 170 cm. The woman had a family history of short stature. Her elder sister had a body height of 148 cm, and her parents had a body height of 145 cm. However, her brother had a body height of 165 cm. Amniocentesis revealed a karyotype of 46,XY. Array comparative genomic hybridization (aCGH) analysis of amniotic fluid revealed a result of arr Xp22.33 (581,803–795,716) × 0–1 mat with a 213.9-kb Xp22.33 microdeletion encompassing only one Online Mendelian Inheritance in Man (OMIM) gene of short stature homeobox (SHOX). Multiplex ligation-dependent probe amplification-P018 (SALSA MLPA Probemix P018 SHOX; MRC-Holland, Amsterdam, The Netherlands) analysis of the DNA extracted from the amniotic fluid and parental blood confirmed maternal transmission of the heterozygous SHOX deletion. The father did not have any SHOX deletion. The mother had a karyotype of 46,XX. An aCGH analysis of the DNA extracted from the maternal blood using CytoChip ISCA Array (Illumina, San Diego, CA, USA) revealed a result of arr Xp22.33 (553,160–1,232,886) × 1.3 with a 679.7-kb Xp22.33 microdeletion encompassing four genes including the OMIM gene of SHOX (Figure 1). The father had a karyotype of 46,XY. An aCGH analysis of the DNA extracted from the paternal blood revealed a result of arr (1–22) × 2, X × 1, Y × 1. The prenatal ultrasound findings were unremarkable. The parents elected to continue the pregnancy, and a normal male baby was delivered at 39 weeks of gestation with a body weight of 3126 g (>97th centile), body length of 49.5 cm (25–50th centile), head circumference of 32.5 cm (5–15th centile), and chest circumference of 31 cm. The cord blood had a karyotype of 46,XY. An aCGH analysis of the cord blood revealed a result of arr Xp22.33 (581,741–1,232,886) × 0.7 with a 651.1-kb Xp22.33 microdeletion encompassing four genes including the OMIM gene of SHOX (Figure 2). Metaphase fluorescence in situ hybridization analysis of 20 cultured lymphocytes obtained from the cord blood using the bacterial artificial chromosome probes RP11-808D8 (877,516–1,060,527) specific for Xpter (Xp22.33) crossing over with Ypter (Yp11.2) and RP11-943J20 (Xq11.1; 63,613,179–63,792,988) showed an Xp22.33 deletion, but no Yp11.2 deletion, in all 20 cells (Figure 3). Metaphase fluorescence in situ hybridization analysis of 20 cultured lymphocytes obtained from the maternal peripheral blood using the bacterial artificial chromosome probes RP11-808D8 and RP11-943J20 showed a heterozygous Xp22.33 deletion in all 20 cells (Figure 4).