Prenatal diagnosis of Bardet‑Biedl syndrome due to novel variants in the BBS10 gene in a fetus with multiple anomalies: A case report

Abstract

Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by obesity, mental retardation, retinal dystrophy, hypogenitalism and renal and polydactyly malformations. The last two malformations may be observed antenatally and are highly variable, making the prenatal diagnosis of BBS challenging. The present study investigated the molecular etiology of BBS and validated a method for prenatal diagnosis. A Chinese couple who had conceived two fetuses with multiple malformations, including hyperechogenic kidneys, polydactyly, cardiac malformation and abdominal abnormalities, presented at the Prenatal Diagnosis Center of Boai Hospital of Zhongshan Affiliated to Southern Medical University (Zhongshan, China) in November 2018. BBS was suspected and whole-exome sequencing was performed for the second fetus. Two novel compound heterozygous variants were detected in the BBS10 gene, c.784_785delGA from the father and c.1812dupT from the mother, which are probably causative of the pathogenesis of BBS. This finding provided a basis for genetic counseling and prenatal diagnosis for the couple and enriched the variation spectrum of the BBS10 gene. The ultrasonic findings of the fetal abdomen are the first reported in fetuses with BBS, expanding the antenatal phenotypes of BBS.

Review of the phenotypes and genotypes of Bardet-Biedl syndrome from China

“…In this series, 11 fetuses were diagnosed prenatally from 2019 to 2022 years ( Li et al, 2019 ; Qiang et al, 2019 ; Li et al, 2020 ; Jing et al, 2021 ; Cai et al, 2022 ; Dong et al, 2022 ; Yan et al, 2022 ) except for one patient reported in 2004 ( Hou, 2004 ). All fetuses presented abnormal kidney images and/or bilateral enlarged hyperechogenic kidneys that implied renal cysts, and one presented hydrometrocolpos and postaxial polydactyly with vaginal atresia ( Hou, 2004 ).…”

“…Among 153 patients ( Supplementary Table S1 ), there were 87 males, 53 females, and 13 unknown (including fetuses) ( Li et al, 2019 ; Qiang et al, 2019 ; Li et al, 2020 ; Jing et al, 2021 ; Cai et al, 2022 ; Dong et al, 2022 ; Tang et al, 2022 ; Yan et al, 2022 ). Among 124 patients with diagnostic age (also excluding 10 fetuses), their age ranged from 1.2 to 44 years old with a mean of 16.70 ± 9.90 years old.…”

“…Malnutrition, anemia, convulsion, dyskinesia, fever and cough, weakness, hypertension, and hyperglycemia were also reported. Among 11 fetuses ( Hou, 2004 ; Li et al, 2019 ; Qiang et al, 2019 ; Li et al, 2020 ; Jing et al, 2021 ; Cai et al, 2022 ; Dong et al, 2022 ; Yan et al, 2022 ), polydactyly and/or abnormal renal images were found by pregnancy examination, and hydrometrocolpos and vaginal atresia were reported in one fetus ( Hou, 2004 ).…”

“…Among 11 fetuses, 10 patients were reported in the last 4 years except for one reported in 2004 years ( Hou, 2004 ). There were 6 patients (54.55%) with BBS7 ( Li et al, 2019 ; Li et al, 2020 ; Jing et al, 2021 ), 3 (27.27%) with BBS1 ( Qiang et al, 2019 ; Cai et al, 2022 ; Yan et al, 2022 ), one with BBS6/ MKKS ( Hou, 2004 ), and one with BBS10 ( Dong et al, 2022 ).…”

“…Among 10 BBS10 patients ( Lin et al, 2018 ; Wang et al, 2018 ; Tao et al, 2020 ; Liu et al, 2021 ; Li et al, 2022a ; Li et al, 2022b ; Dong et al, 2022 ; Lu et al, 2022 ; Tao et al, 2022 ; Yan et al, 2022 ), 7 had compound heterozygous variants and 3 had homozygous variants. A total of 11 variants were also reported.…”