Genetic counseling of prenatally detected familial 15q13.2q13.3 microdeletion encompassing CHRNA7 and OTUD7A with asymptomatic carriers in the family

Objective

A case of prenatal diagnosis of familial 15q13.2q13.3 microdeletion is presented.

Case report

A 35-year-old, gravida 2, para 1, woman was referred for genetic counseling because of 15q13.2q13.3 microdeletion in the fetus and the mother. The carrier mother was asymptomatic and normal in phenotype. The woman underwent amniocentesis at 17 weeks of gestation because of short nasal bone on fetal ultrasound. Amniocentesis revealed a karyotype of 46,XX. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr [GRCh37] 15q13.2q13.3 (30,954,726–32,509,926) × 1 with a 1.56-Mb 15q13.2q13.3 microdeletion encompassing six OMIM genes of FAN1, TRPM1, MIR211, KLF13, OTUD7A and CHRNA7. Prenatal ultrasound was normal. The woman had a 4-year-old healthy daughter. Four years ago, during her first pregnancy, she underwent expanded non-invasive prenatal testing (NIPT) in the first trimester, and the result was 15q13.2q13.3 deletion. Subsequent amniocentesis revealed a karyotype of 46,XX, and aCGH analysis on uncultured amniocytes revealed no genomic imbalance. However, no further genetic test in the woman and her husband had been made. Therefore, the woman was not aware of her carrier status when she was pregnant again. During this pregnancy, subsequent aCGH analysis on the parental bloods revealed a 1.56-Mb 15q13.2q13.3 microdeletion in the mother and no genomic imbalance in the father. The woman was hesitant to keep the baby. However, following the genetic counseling, the woman's parents were advised to receive genetic testing for 15q13.2q13.3 microdeletion. The 68-year-old asymptomatic healthy grandfather carried the same 15q13.2q13.3 microdeletion, and the grandmother did not have such a microdeletion. The woman finally decided to continue the pregnancy, and a healthy 2750-g baby was delivered at term with no phenotypic abnormalities.

Conclusion

Familial 15q13.2q13.3 microdeletion may present no phenotypic abnormalities in three generations.