Abstract

Background Bardet–Biedl syndrome (BBS) is a rare multisystem developmental disorder. In this study, we report the genetic causes and clinical manifestations in two Chinese families with BBS. Materials and Methods Two families were recruited in this study. Family A was a four-generation family with four affected and 15 unaffected members participating in the study, and family B was a consanguineous family with one affected and three unaffected members participating. Whole exome sequencing was performed in the two families, followed by a multistep bioinformatics analysis. Sanger sequencing was used to verify the variants and to perform a segregation analysis. Comprehensive ocular and systemic examinations were also conducted. Results Novel compound heterozygous variants c.235T > G (p.T79P) and c.534 + 1G > T were detected in the BBS2 gene in family A, and known homozygous variant c.748G > A (p.G250R) was detected in the MKKS gene in family B. Both families presented with retinitis pigmentosa; however, except for polydactyly, all other systemic manifestations were different. All of the affected family members in family A were overweight with a high body mass index (range from 26.5 to 41.9) and high blood pressure. Family A also presented with a delay in the onset of secondary sex characteristics and genital anomalies, while other systemic abnormalities were absent in family B. Conclusions This study presents one family with two novel BBS2 variants, expanding the variant spectrum of BBS, and one family with a known homozygous MKKS variant. The different phenotypes seen between the families with BBS2 and MKKS variants will contribute to the literature and our overall understanding of BBS.

Highlights

  • We report on two Chinese families with Bardet–Biedl syndrome (BBS), including their gene variants and clinical manifestations

  • Whole exome sequencing (WES) was performed in six family members (III : 4, III : 5, IV : 1, IV : 5, IV : 8, and IV : 10) of family A

  • Sanger sequencing was performed in all of the available family members, which confirmed that all the affected members had the compound heterozygous variants and the unaffected members had no more than one of the two variants (Figure 1)

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Summary

Introduction

Bardet–Biedl syndrome (BBS; MIM: 209900) is a rare multisystem developmental disorder with a prevalence of 1 : 13,500 to 1 : 160,000 [1, 2]. e characteristics of BBS include rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotropic hypogonadism, complex female genitourinary malformations, and renal abnormalities [3].According to the Retinal Information Network (RetNet; https://sph.uth.edu/retnet/sum-dis.htm),a total of 26 genes, including ADIPOR1 (MIM: 607945) [4], ARL6 (MIM: 608845) [5], BBIP1 (MIM: 613605) [6], BBS1 (MIM: 209901) [7], BBS2 (MIM: 615981) [8], BBS4 (MIM: 615982) [9], BBS5(MIM: 603650) [10], BBS7 (MIM: 607590) [11], BBS9 (MIM: 607968) [12], BBS10 (MIM: 615987) [13], BBS12 (MIM: 615989) [14], C8orf (MIM: 614477) [15], CEP290 (MIM: 610142) [16], IFT172 (MIM: 607386) [17], IFT27 (MIM: 615870) [18], INPP5E (MIM: 613037) [19], KCNJ13 (MIM: 603208) [20], LZTFL1 (MIM: 606568) [21], MKKS (MIM: 604896) [22], MKS1 (MIM: 609883) [23], NPHP1 (MIM: 607100) [24], SDCCAG8 (MIM: 613524) [25], TRIM32 (MIM: 602290) [26], TTC8 (MIM: 608132) [27], SCLT1 (MIM: 611399), and CEP164 (MIM: 614848) [28], have currently been reported to cause BBS.In this study, we report on two Chinese families with BBS, including their gene variants and clinical manifestations.Journal of Ophthalmology. We report on two Chinese families with BBS, including their gene variants and clinical manifestations. Novel compound heterozygous variants c.235T > G (p.T79P) and c.534 + 1G > T were detected in the BBS2 gene in family A, and known homozygous variant c.748G > A (p.G250R) was detected in the MKKS gene in family B. Both families presented with retinitis pigmentosa; except for polydactyly, all other systemic manifestations were different. Is study presents one family with two novel BBS2 variants, expanding the variant spectrum of BBS, and one family with a known homozygous MKKS variant. Conclusions. is study presents one family with two novel BBS2 variants, expanding the variant spectrum of BBS, and one family with a known homozygous MKKS variant. e different phenotypes seen between the families with BBS2 and MKKS variants will contribute to the literature and our overall understanding of BBS

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