Introduction

Genetic counseling of prenatally detected familial 15q13.2q13.3 microdeletion remains difficult. Here, we present such a case.

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] (X) × 2, 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 ( Fig. 1 ), 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.

(A) and (B) Array comparative genomic hybridization analysis on the DNA extracted from the asymptomatic healthy grandfather using SurePrint G3 Unrestricted CGH ISCA v2, 8 × 60 K Array (Agilent Technologies, Santa Clara, CA, USA) shows 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 OTUD7A and CHRNA7 .

Discussion

The present case was associated with a false-positive result of NIPT due to maternal 15q13.2q13.3 microdeletion. False-positive result of NIPT results have been reported in 0.3 % of the cases because of confined placental mosaicism, maternal mosaicism, maternal copy number variations (CNVs), statistic chance as the cut-off for a positive test, maternal transfusion, vanishing twins and maternal malignancy [ ]. In the present case, a maternal genetic test should have been performed to elucidate the presence of maternal 15q13.2q13.3 microdeletion during the first pregnancy. This is necessary for genetic counseling in the further pregnancies.

Genetic counseling can be difficult if the asymptomatic carrier mother who carries the same microdeletion as the fetus is hesitant to keep the baby. Chromosome 15q13.3 deletion syndrome (OMIM 612001 ) is associated with a highly variable phenotype, even within families segregating the same deletion, and individuals with 15q13.3 deletion syndrome may show mild to moderate mental retardation or learning difficulties, developmental delay, behavioral disorders, epilepsy and various dysmorphic features of the face and digits [ ].

The present case had haploinsufficiency of CHRNA7 and OTUD7A which have been reported to be the critical region associated with 15q13.3 deletion syndrome [ ]. The present case was associated with asymptomatic carrier mother and grandfather. Chromosome 15q13.3 deletion syndrome has been found to be inherited in about 75 % of the cases with the association of apparently normal individuals including incomplete penetrance [ ]. Genetic investigation of carrier family members and analysis of their phenotypes may help the parents to make a decision to keep the baby under such a circumstance.

In summary, we present a case of prenatal diagnosis of familial 15q13.2q13.3 microdeletion. Familial 15q13.2q13.3 microdeletion may present no phenotypic abnormalities in the family members of three generations.