A case of Bardet-Biedl syndrome caused by a recurrent variant in BBS12: A case report

Abstract

Bardet-Biedl syndrome (BBS) is a clinically and genetically heterogenous disorder that manifests as a result of primary cilia impairment. Cilia are present on most cell types, thus BBS is a multisystemic condition involving the majority of organ systems. The core features of the syndrome include retinal degeneration, obesity, polydactyly, cognitive impairment, renal anomalies and urogenital malformations. To date, pathogenic variants in 26 genes have been shown to be involved in the molecular basis of this rare ciliopathy. Of these causal loci, BBS12 accounts for ~8% of all cases. In this case report, an individual with BBS caused by a rare recurrent variant in BBS12 (NM_152618.3: c.1063C>T; p.Arg355^*) is described and compared with others with the same DNA variant, placing this finding in the context of the current literature.

Keywords: Bardet-Biedl syndrome; chaperonin; cilia; ciliopathies; oligogenic; pleiotropy.

Figure 1

Location and interaction of BBS proteins within cilium. (A) Overview of BBS protein complexes at the cilium. (B) Details of anterograde transport molecule assembly. The BBS proteins are shown in bold. BBS, Bardet-Biedl syndrome.

Figure 2

Images of the presented case. Images of the patient at (A-E) 5 and (B) 6 years-old, showing: (A) Tooth anomalies and dysmorphic craniofacial features, such as narrow forehead, decreased bitemporal diameter, sparse eyebrows, long and smooth philtrum and full cheeks; (B) Obesity; (C-E) scars and (C and D) reminiscent bone deformity after removal of polydactyly (black arrows); (D) brachydactyly, conic fingers, hypoplasia of distal phalanges and hypoplastic nails; and (E) partial cutaneous syndactyly of the second and third toes, and hypoplastic nails.

Figure 3

Pedigree and segregation analysis of BBS12 NM_152618.3: c.1063C>T, p.Arg355^*. (A) Pedigree of the family. White shapes, unaffected; black shapes, affected; squares, males; circles, females. The genotype of the BBS variant are shown. (B) Chromatograms showing sequence traces flanking the c.1063C>T variant. Both parents are heterozygous and the proband is homozygous for the pathogenic change. WT, wild type; BBS, Bardet-Biedl syndrome.