Bardet Biedl综合征的诊治进展
Progress in diagnosis and treatment of Bardet Biedl syndrome
Received date: 2022-10-08
Online published: 2024-02-02
Bardet Biedl综合征(BBS)是一种罕见的累及多系统的常染色体隐性遗传病，主要特征为视网膜病变、多指（趾）畸形、肥胖、智力低下、性腺发育不良和肾功能异常。迄今已明确26种致病基因，均定位于初级纤毛上，其中BBS1、BBS2和BBS10是最常见的变异基因。对于该疾病目前尚无治愈性疗法，主要以对症支持治疗为主。本文从临床特点、诊断标准、致病基因、我国BBS患者现状、治疗等角度对该疾病进行综述，以期为临床对此类疾病的诊治提供参考。
关键词： Bardet Biedl综合征; 诊断标准; 致病基因; 治疗
林娇 , 徐鑫星 , 王传凯 , 蒋丽琼 综述 , 王春林 审校 . Bardet Biedl综合征的诊治进展[J]. 临床儿科杂志, 2024 , 42(2) : 157 -163 . DOI: 10.12372/jcp.2024.22e1314
The Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder affecting multiple systems, primarily manifesting as retinal lesions, polydactylism (or hyperdactylism), obesity, intellectual diminution, sexual duct development deficiency, and renal abnormalities. To date, 26 disease-causing genes have been identified, all of which are localised to the primary cilia, with the BBS1, BBS2 and BBS10 genes being the most common genetic causes. There is no curative therapy for this disease, and symptomatic supportive treatment is the main focus. This paper reviews the disease from the perspectives of clinical characteristics, diagnostic criteria, causative genes, the current situation of BBS patients in China, and treatment, with a view to providing reference for the clinical diagnosis and treatment of this disease.
Key words： Bardet Biedl syndrome; diagnostic criteria; pathogenic gene; management
| [1] | Priya S, Nampoothiri S, Sen P, et al. Bardet-Biedl syndrome: genetics, molecular pathophysiology, and disease management[J]. Indian J Ophthalmol, 2016, 64(9): 620-627. |
| [2] | Caba L, Florea L, Braha EE, et al. Monitoring and management of Bardet-Biedl syndrome: what the multi-disciplinary team can do[J]. J Multidiscip Healthc, 2022, 15: 2153-2167. |
| [3] | Pomeroy J, Krentz A D, Richardson JG, et al. Bardet-Biedl syndrome: weight patterns and genetics in a rare obesity syndrome[J]. Pediatr Obes, 2021, 16(2): e12703. |
| [4] | Moore SJ, Green JS, Fan Y, et al. Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study[J]. Am J Med Genet A, 2005, 132A(4): 352-360. |
| [5] | Tsang SH, Aycinena ARP, Sharma T. Ciliopathy: Bardet-Biedl syndrome[J]. Adv Exp Med Biol, 2018, 1085: 171-174. |
| [6] | Melluso A, Secondulfo F, Capolongo G, et al. Bardet-Biedl syndrome: current perspectives and clinical outlook[J]. Ther Clin Risk Manag, 2023, 19: 115-132. |
| [7] | Kerr EN, Bhan A, Heon E. Exploration of the cognitive, adaptive and behavioral functioning of patients affected with Bardet-Biedl syndrome[J]. Clin Genet, 2016, 89(4): 426-433. |
| [8] | Marchese E, Ruoppolo M, Perna A, et al. Exploring key challenges of understanding the pathogenesis of kidney disease in Bardet-Biedl syndrome[J]. Kidney Int Rep, 2020, 5(9): 1403-1415. |
| [9] | Forsythe E, Sparks K, Best S, et al. Risk factors for severe renal disease in Bardet-Biedl syndrome[J]. J Am Soc Nephrol, 2017, 28(3): 963-970. |
| [10] | Pomeroy J, Offenwanger KM, Timmler T. Diabetes mellitus in Bardet Biedl syndrome[J]. Curr Opin Endocrinol Diabetes Obes, 2023, 30(1): 27-31. |
| [11] | Niederlova V, Modrak M, Tsyklauri O, et al. Meta-analysis of genotype-phenotype associations in Bardet-Biedl syndrome uncovers differences among causative genes[J]. Hum Mutat, 2019, 40(11): 2068-2087. |
| [12] | Jeziorny K, Antosik K, Jakiel P, et al. Next-generation sequencing in the diagnosis of patients with Bardet-Biedl syndrome-new variants and relationship with hyperglycemia and insulin resistance[J]. Genes (Basel), 2020, 11(11):1283. |
| [13] | Florea L, Caba L, Gorduza EV. Bardet-Biedl syndrome-multiple kaleidoscope images: insight into mechanisms of genotype-phenotype correlations[J]. Genes (Basel), 2021, 12(9):1353. |
| [14] | Patel MM, Tsiokas L. Insights into the regulation of ciliary disassembly[J]. Cells, 2021, 10(11):2977. |
| [15] | McConnachie DJ, Stow JL, Mallett AJ. Ciliopathies and the kidney: a review[J]. Am J Kidney Dis, 2021, 77(3): 410-419. |
| [16] | Yan X, Shen Y. Rab-like small GTPases in the regulation of ciliary Bardet-Biedl syndrome (BBS) complex transport[J]. FEBS J, 2022, 289(23): 7359-7367. |
| [17] | Wingfield JL, Lechtreck KF, Lorentzen E. Trafficking of ciliary membrane proteins by the intraflagellar transport/BBSome machinery[J]. Essays Biochem, 2018, 62(6): 753-763. |
| [18] | Prasai A, Cernohorska MS, Ruppova K, et al. The BBSome assembly is spatially controlled by BBS1 and BBS4 in human cells[J]. J of Biol Chem, 2020, 295(42): 14279-14290. |
| [19] | Guo DF, Merrill RA, Qian L, et al. The BBSome regulates mitochondria dynamics and function[J]. Mol Metab, 2022, 67: 101654. |
| [20] | Zhang Q, Seo S, Bugge K, et al. BBS proteins interact genetically with the IFT pathway to influence SHH-related phenotypes[J]. Hum Mol Genet, 2012, 21(9): 1945-1953. |
| [21] | Katagiri S, Hosono K, Hayashi T, et al. Novel biallelic splice-site BBS1 variants in Bardet-Biedle syndrome: a case report of the first Japanese patient[J]. Doc Ophthalmol, 2020, 141(1): 77-88. |
| [22] | Schaefer E, Durand M, Stoetzel C, et al. Molecular diagnosis reveals genetic heterogeneity for the overlapping MKKS and BBS phenotypes[J]. Eur J Med Genet, 2011, 54(2): 157-160. |
| [23] | Singh SK, Gui M, Koh F, et al. Structure and activation mechanism of the BBSome membrane protein trafficking complex[J]. Elife, 2020, 9 : e53322. |
| [24] | Gupta N, D'Acierno M, Zona E, et al. Bardet-Biedl syndrome: the pleiotropic role of the chaperonin-like BBS6, 10, and 12 proteins[J]. Am J Med Genet C Semin Med Genet, 2022, 190(1): 9-19. |
| [25] | Ohto T, Enokizono T, Tanaka R, et al. A novel BBS10 mutation identified in a patient with Bardet-Biedl syndrome with a violent emotional outbreak[J]. Hum Genome Var, 2017, 4: 17033. |
| [26] | Wang L, Liu Y, Stratigopoulos G, et al. Bardet-Biedl syndrome proteins regulate intracellular signaling and neuronal function in patient-specific iPSC-derived neurons[J]. J Clin Invest, 2021, 131(8): e146287. |
| [27] | Chandra B, Tung M L, Hsu Y, et al. Retinal ciliopathies through the lens of Bardet-Biedl syndrome: past, present and future[J]. Prog Retin Eye Res, 2022, 89: 101035. |
| [28] | Feuillan PP, Ng D, Han JC, et al. Patients with Bardet-Biedl syndrome have hyperleptinemia suggestive of leptin resistance[J]. J Clin Endocrinol Metab, 2011, 96(3): E528-E535. |
| [29] | Imhoff O, Marion V, Stoetzel C, et al. Bardet-Biedl syndrome: a study of the renal and cardiovascular phenotypes in a French cohort[J]. Clin J Am Soc Nephrol, 2011, 6(1): 22-29. |
| [30] | Meyer J R, Krentz AD, Berg RL, et al. Kidney failure in Bardet-Biedl syndrome[J]. Clin Genet, 2022, 101(4): 429-441. |
| [31] | Yan K, Sun Y, Yang Y, et al. Case report: identification pathogenic abnormal splicing of BBS1 causing Bardet-Biedl syndrome type I (BBS1) due to missense mutation[J]. Front Genet, 2022, 13: 849562. |
| [32] | Deng L, Liu Y, Yuan M, et al. Prenatal diagnosis and outcome of fetal hyperechogenic kidneys in the era of antenatal next-generationsequencing[J]. Clin Chim Acta, 2022, 528: 16-28. |
| [33] | Cai M, Lin M, Lin N, et al. Novel homozygous nonsense mutation associated with Bardet-Biedl syndrome in fetuses with congenital renal malformation[J]. Medicine (Baltimore), 2022, 101(32): e30003. |
| [34] | Jing XY, Jiang F, Li DZ. Unmasking a recessive allele by a deletion: early prenatal diagnosis of Bardet-Biedl syndrome in a Chinese family[J]. Congenit Anom (Kyoto), 2021, 61(4): 138-139. |
| [35] | 李博红, 谢建生, 耿茜, 等. BBS7基因突变致Bardet-Biedl综合征胎儿/引产儿的基因诊断:两例报道[J]. 中华围产医学杂志, 2020, 23(6): 380-386. |
| [36] | 钱雯, 王正蓉, 张競之, 等. BBS1基因新突变导致Bardet-Biedl综合征的遗传学分析及产前诊断[J]. 中国循证儿科杂志, 2019, 14(6): 467-469. |
| [37] | Li QY, Huang LY, Li DZ. Early prenatal detection of Bardet-Biedl syndrome in a case with postaxial polydactyly and hyperechoic kidneys confirmed by next generation sequencing[J]. Congenit Anom (Kyoto), 2019, 59(4): 142-144. |
| [38] | Seo S, Mullins RF, Dumitrescu AV, et al. Subretinal gene therapy of mice with Bardet-Biedl syndrome type 1[J]. Invest Ophthalmol Vis Sci, 2013, 54(9): 6118-6132. |
| [39] | Simons DL, Boye SL, Hauswirth WW, et al. Gene therapy prevents photoreceptor death and preserves retinal function in a Bardet-Biedl syndrome mouse model[J]. Proc Natl Acad Sci U S A, 2011, 108(15): 6276-6281. |
| [40] | Cring MR, Meyer KJ, Searby CC, et al. Ectopic expression of BBS1 rescues male infertility, but not retinal degeneration, in a BBS1 mouse model[J]. Gene Ther, 2022, 29(5): 227-235. |
| [41] | Haws R, Brady S, Davis E, et al. Effect of setmelanotide, a melanocortin-4 receptor agonist, on obesity in Bardet-Biedl syndrome[J]. Diabetes Obes Metab, 2020, 22(11): 2133-2140. |
| [42] | Haqq AM, Chung WK, Dollfus H, et al. Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alstrom syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period[J]. Lancet Diabetes Endocrinol, 2022, 10(12): 859-868. |
| [43] | Tobin JL, Beales PL. Restoration of renal function in zebrafish models of ciliopathies[J]. Pediatr Nephrol, 2008, 23(11): 2095-2099. |
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