OBJECTIVE: To carry out genetic testing on two fetuses with prenatal ultrasound finding of polydactyly and renal abnormalities to determine the underlying causes. METHODS: Two fetuses with structural abnormalities detected by prenatal ultrasound at Cangzhou People's Hospital in 2021 were selected as the study subjects. Genomic DNA was extracted from the muscle tissue of the abortus and peripheral blood samples from both parents. Whole-exome sequencing (WES) was conducted on the trio to detect the genetic variants. Quantitative PCR was used to validate the exonic deletions. This study has been approved by the Ethics Committee of Cangzhou People's Hospital (Ethics No.K2020-049). RESULTS: Prenatal ultrasound revealed postaxial polydactylies of fingers and toes and slightly enlarged kidneys with increased echogenicity in fetus 1, along with polydactyly of both hands, enlarged kidneys, and enhanced echogenicity of renal parenchyma in fetus 2. Trio-WES analysis revealed that fetus 1 has harbored a pathogenic c.1339G>A variant of the BBS1 gene, along with a heterozygous 426 bp deletion in the 11q13.2 region, which was unreported previously. The deletion has involved exons 10 and 11 of the BBS1 gene. The two variants were inherited from its mother and father, respectively. Fetus 2 was found to harbor a pathogenic c.539G>A variant and a likely pathogenic c.49G>A variant of the BBS10 gene, which were inherited from its mother and father, respectively. The c.49G>A variant has not been documented in databases and the literature. CONCLUSION Two rare fetuses with Bardet-Biedl syndrome have been diagnosed. Above finding has expanded the mutational spectrum of this syndrome and has important implications for genetic counseling for the affected families.
Humans ; Bardet-Biedl Syndrome/diagnostic imaging* ; Female ; Pregnancy ; Fetus/abnormalities* ; Ultrasonography, Prenatal ; Phenotype ; Polydactyly/diagnostic imaging* ; Exome Sequencing ; Adult ; Genetic Testing ; Male ; Prenatal Diagnosis ; Group II Chaperonins/genetics* ; Microtubule-Associated Proteins

OBJECTIVETo study the clinical characteristics and diagnostic methods of rare autosomal recessive inherited Bardet-Biedl syndrome in patients presented with renal abnormalities.

METHODComprehensive analyses were performed on data of 4 confirmed Bardet-Biedl syndrome cases seen at nephrology department of Beijing Children Hospital affiliated to Capital Medical University, including clinical features, laboratory examination and diagnostic criteria.

RESULT(1) Four cases were confirmed to meet Bardet-Biedl syndrome diagnostic criteria (male: female = 1: 1): first diagnosis age was 10 y, 9 y 8 m, 10 y 10 m, 8 y 2 m. (2) Cases 1, 2, and 3 had a history of polyuria and polydipsia, cases 4 began with edema and oliguria. (3) All had slight change in urine routine test. Case 3 and Case 4 were presented with small to medium amount of proteinuria. None had microscopic hematuria. (4) All had different degree of renal injury, Case 1 and 3 were at the third phase of chronic kidney disease (CKD), Case 4 was at the fourth phase of CKD, Case 4 was at the fifth phase of CKD and needed dialysis. (5) All cases had obvious abnormalities of urinary tract ultrasound, 3 of them had chronic diffuse lesions with cyst formation of both kidneys. The rest one had dysplasia of right kidney and fused kidney. (6) All cases were presented with vision loss with 100% of electroretinogram abnormalities and 50% of fundus examination abnormalities. (7) Three cases were presented with obesity. (8) Multiple organs were involved in all cases, including electrocardiographic abnormality and/or thickening of the left ventricular wall (4/4) , polydactyly (2/4) , small penis and testicles (2/4) and short stature (2/4) .

CONCLUSIONClinical manifestations of Bardet-Biedl syndrome (BBS) conceals, routine urine test changes slightly, abnormalities of renal structure and (or) tubular interstitial function is a typical manifestation of children with BBS. Urinary tract ultrasound screening may show diffuse lesions with double kidney with cyst formation or structural abnormalities. Clinical manifestation accompany with retinal degeneration, obesity, myocardial involvement, polydactyly, and hypogonadism.

Abnormalities, Multiple ; Bardet-Biedl Syndrome ; complications ; diagnosis ; pathology ; Biomarkers ; blood ; urine ; Child ; Female ; Humans ; Intellectual Disability ; Kidney ; abnormalities ; diagnostic imaging ; Kidney Diseases ; diagnosis ; etiology ; pathology ; Male ; Renal Insufficiency ; etiology ; pathology ; Retinal Diseases ; etiology ; pathology ; Tomography, X-Ray Computed ; Ultrasonography, Doppler, Color