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Prenatal diagnosis of fetuses with region of homozygosity detected by single nucleotide polymorphism array: a retrospective cohort study


Region of homozygosity (ROH) is classified as uniparental disomy (UPD) or identity by descent, depending on its origin. To explore the clinical relevance of ROH in prenatal diagnoses, we reviewed 5063 fetal samples subjected to single nucleotide polymorphism array at our center over 5 years. ROH cases meeting our reporting threshold were further analyzed. ROHs were detected in 22 fetuses (0.43%, 22/5063), of which, 77.3% (17/22) showed a ROH on a single chromosome and 22.7% (5/22) showed multiple ROHs on different chromosomes. Among 5063 fetuses undergoing invasive prenatal diagnoses owing to various indications, five cases were identified as UPDs with a rate of ~1/1000. We observed clinically relevant UPDs in two cases related to Prader–Willi syndrome and transient neonatal diabetes mellitus. Of note, one case showed 50% mosaicism for trisomy 2 in amniotic fluid, whereas a complete UPD (2) was observed in umbilical cord blood. Trio whole-exome sequencing was performed for three cases. Clinically relevant variants were identified in two cases, one of which, NM_000302:c.2071_2072insCC (p.R693Qfs*122) in PLOD1 located in the ROH, may be related to Ehlers-Danlos syndrome, kyphoscoliotic type, 1. Overall, 72.7% (16/22) of the ROH carriers showed ultrasound abnormalities, of whom eight (50%, 8/16) had adverse perinatal outcomes. Our study demonstrates that the clinical relevance of ROHs should be examined regarding fetuses with ROHs occurring on imprinted chromosomes or those derived from consanguineous parents in prenatal diagnoses; imprinting disorders and/or autosomal recessive diseases attributed to ROHs should be considered during genetic counseling.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.


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We deeply thank the patients and family members who participated in this study.


This work was supported by grant from Fujian Provincial Health Technology Project (grant no. 2020GGB018); Fujian Provincial Maternity and Child Health Hospital (grant no. YCXM 19–15); Fujian Provincial Natural Science Foundation (grant no. 2019J01509); and Joints Funds for the Innovation of Science and Technology, Fujian Province (grant no. 2020Y9159).

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Correspondence to Na Lin, Hailong Huang or Liangpu Xu.

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Liang, B., Yu, D., Zhao, W. et al. Prenatal diagnosis of fetuses with region of homozygosity detected by single nucleotide polymorphism array: a retrospective cohort study. J Hum Genet (2022).

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