Epidemiological Characteristics of Patients with Hutchinson-Gilford Progeria Syndrome and Progeroid Laminopathies in China

Overview

Journal Pediatr Res

Specialties Biology
Pediatrics

Date 2024 Jan 9

PMID 38191824

Authors

Jingjing Wang

Qinmei Yu

Xiaoxiao Tang

Leslie B Gordon

Junyi Chen

Buchun Jiang

Guoping Huang

Haidong Fu

Jianqin Qian

Zhihong Liu

Jianhua Mao

Affiliations

Soon will be listed here.

Abstract

Background: Hutchinson-Gilford progeria syndrome (HGPS) and progeroid laminopathies (PL) are extremely rare genetic diseases with extremely poor prognoses. This study aims to investigate the epidemiological and genotypic characteristics of patients with HGPS/PL in China.

Methods: Using a cross-sectional study design, general characteristics and genotypic data of 46 patients with HGPS/PL from 17 provinces in China were analyzed.

Results: Among the 46 patients with HGPS/PL, 20 patients are HGPS, and the rest are PL; the identified total prevalence of HGPS/PL is 1/23 million. Among 42 patients with gene reports, 3 carried compound heterozygous mutations in the ZMPSTE24 while the other 39 carried LMNA mutations. Among PL, LMNA c.1579 C > T homozygous mutation was the most common. The onset of classic genotype HGPS is skin sclerosis in the first month after birth. The primary clinical manifestations of PL patients include skin abnormalities, growth retardation, and joint stiffness. The median age of onset for PL was 12 (6,12) months.

Conclusions: In China, the identified total prevalence of HGPS/PL is 1/23 million. 92.8% of the genetic mutations of HGPS/PL were located in LMNA, and the rest in ZMPSTE24. Most patients of HGPS/PL have skin abnormalities as the earliest manifestation. Compared to PL, the classic genotype HGPS starts earlier.

Impact Statement: Hutchinson-Gilford progeria syndrome (HGPS) and progeroid laminopathies (PL) are extremely rare genetic diseases with extremely poor prognoses. To date, there is a paucity of epidemiological data related to HGPS/PL in China. This study first examined the genotypic, phenotypic, and prevalence characteristics of 40-50% of the cases of HGPS/PL in mainland China through a collaborative international registry effort. In China, the identified total prevalence of HGPS/PL is 1/23 million. 92.8% of the genetic mutations of HGPS/PL are located in LMNA. LMNA c.1579 C > T homozygous mutations are the most common form of gene mutations among the Chinese PL population.

Citing Articles

Epidemiology and distribution of 207 rare diseases in China: A systematic literature review.

Wang Y, Liu Y, Du G, Liu Y, Zeng Y Intractable Rare Dis Res. 2024; 13(2):73-88.

PMID: 38836174 PMC: 11145401. DOI: 10.5582/irdr.2024.01001.

References

De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I . Lamin a truncation in Hutchinson-Gilford progeria. Science. 2003; 300(5628):2055. DOI: 10.1126/science.1084125. View

Eriksson M, Brown W, Gordon L, Glynn M, Singer J, Scott L . Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003; 423(6937):293-8. PMC: 10540076. DOI: 10.1038/nature01629. View

Coppede F . Mutations Involved in Premature-Ageing Syndromes. Appl Clin Genet. 2021; 14:279-295. PMC: 8180271. DOI: 10.2147/TACG.S273525. View

Guardiani E, Zalewski C, Brewer C, Merideth M, Introne W, Smith A . Otologic and audiologic manifestations of Hutchinson-Gilford progeria syndrome. Laryngoscope. 2011; 121(10):2250-5. PMC: 3688450. DOI: 10.1002/lary.22151. View

Gordon L, Massaro J, DAgostino Sr R, Campbell S, Brazier J, Brown W . Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome. Circulation. 2014; 130(1):27-34. PMC: 4082404. DOI: 10.1161/CIRCULATIONAHA.113.008285. View

Neilan E . Laminopathies, other progeroid disorders, and aging: common pathogenic themes and possible treatments. Am J Med Genet A. 2009; 149A(4):563-6. DOI: 10.1002/ajmg.a.32702. View

Shin J, Worman H . Molecular Pathology of Laminopathies. Annu Rev Pathol. 2021; 17:159-180. PMC: 8881990. DOI: 10.1146/annurev-pathol-042220-034240. View

Foo M, Ong P, Dreesen O . Premature aging syndromes: From patients to mechanism. J Dermatol Sci. 2019; 96(2):58-65. DOI: 10.1016/j.jdermsci.2019.10.003. View

Ashapkin V, Kutueva L, Kurchashova S, Kireev I . Are There Common Mechanisms Between the Hutchinson-Gilford Progeria Syndrome and Natural Aging?. Front Genet. 2019; 10:455. PMC: 6529819. DOI: 10.3389/fgene.2019.00455. View

10.

Merideth M, Gordon L, Clauss S, Sachdev V, Smith A, Perry M . Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med. 2008; 358(6):592-604. PMC: 2940940. DOI: 10.1056/NEJMoa0706898. View

11.

Zhu L, Liu H, Li D, Li F, Qin X, Li W . [Clinical features and genetic diagnosis of four cases with progeria syndrome]. Zhonghua Er Ke Za Zhi. 2019; 57(8):636-638. DOI: 10.3760/cma.j.issn.0578-1310.2019.08.013. View

12.

Doanh L, Phuong H, Phuong N, Thu L, Thuong N . Mandibuloacral dysplasia in a young Vietnamese girl caused by homozygous missense variant c.1579C>T in the LMNA gene with progeria and severe skin lesions. JAAD Case Rep. 2021; 16:5-8. PMC: 8413666. DOI: 10.1016/j.jdcr.2021.08.011. View

13.

Luo D, Wang X, Meng Y, He D, Chen Y, Ke Z . Mandibuloacral dysplasia type A-associated progeria caused by homozygous LMNA mutation in a family from Southern China. BMC Pediatr. 2014; 14:256. PMC: 4287574. DOI: 10.1186/1471-2431-14-256. View

14.

Agarwal A, Kazachkova I, Ten S, Garg A . Severe mandibuloacral dysplasia-associated lipodystrophy and progeria in a young girl with a novel homozygous Arg527Cys LMNA mutation. J Clin Endocrinol Metab. 2008; 93(12):4617-23. PMC: 2626450. DOI: 10.1210/jc.2008-0123. View

15.

Xiong Z, Lu Y, Xue J, Luo S, Xu X, Zhang L . Hutchinson-Gilford progeria syndrome accompanied by severe skeletal abnormalities in two Chinese siblings: two case reports. J Med Case Rep. 2013; 7:63. PMC: 3602076. DOI: 10.1186/1752-1947-7-63. View

16.

Liang L, Zhang H, Gu X . Homozygous LMNA mutation R527C in atypical Hutchinson-Gilford progeria syndrome: evidence for autosomal recessive inheritance. Acta Paediatr. 2009; 98(8):1365-8. DOI: 10.1111/j.1651-2227.2009.01324.x. View

17.

Schaflinger E, Blatterer J, Khan A, Kaufmann L, Auinger L, Tatrai B . An exceptional biallelic N-terminal frame shift mutation in ZMPSTE24 leads to non-lethal progeria due to possible utilization of a downstream alternative start codon. Gene. 2022; 833:146582. DOI: 10.1016/j.gene.2022.146582. View

18.

Misteli T . Farnesyltransferase inhibition in HGPS. Cell. 2021; 184(2):293. DOI: 10.1016/j.cell.2020.12.029. View

19.

Suzuki M, Jeng L, Chefo S, Wang Y, Price D, Li X . FDA approval summary for lonafarnib (Zokinvy) for the treatment of Hutchinson-Gilford progeria syndrome and processing-deficient progeroid laminopathies. Genet Med. 2022; 25(2):100335. DOI: 10.1016/j.gim.2022.11.003. View

20.

Gordon L, Kleinman M, Massaro J, DAgostino Sr R, Shappell H, Gerhard-Herman M . Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome. Circulation. 2016; 134(2):114-25. PMC: 4943677. DOI: 10.1161/CIRCULATIONAHA.116.022188. View