Dyssegmental dysplasia Rolland-Desbuquois type is caused by pathogenic variants in HSPG2 - a founder haplotype shared in five patients.
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
29 Feb 2024
29 Feb 2024
Historique:
received:
20
11
2023
accepted:
06
02
2024
revised:
17
01
2024
medline:
1
3
2024
pubmed:
1
3
2024
entrez:
29
2
2024
Statut:
aheadofprint
Résumé
Dyssegmental dysplasia (DD) is a severe skeletal dysplasia comprised of two subtypes: lethal Silverman-Handmaker type (DDSH) and nonlethal Rolland-Desbuquois type (DDRD). DDSH is caused by biallelic pathogenic variants in HSPG2 encoding perlecan, whereas the genetic cause of DDRD remains undetermined. Schwartz-Jampel syndrome (SJS) is also caused by biallelic pathogenic variants in HSPG2 and is an allelic disorder of DDSH. In SJS and DDSH, 44 and 8 pathogenic variants have been reported in HSPG2, respectively. Here, we report that five patients with DDRD carried four pathogenic variants in HSPG2: c.9970 G > A (p.G3324R), c.559 C > T (p.R187X), c7006 + 1 G > A, and c.11562 + 2 T > G. Two patients were homozygous for p.G3324R, and three patients were heterozygous for p.G3324R. Haplotype analysis revealed a founder haplotype spanning 85,973 bp shared in the five patients. SJS, DDRD, and DDSH are allelic disorders with pathogenic variants in HSPG2.
Identifiants
pubmed: 38424183
doi: 10.1038/s10038-024-01229-6
pii: 10.1038/s10038-024-01229-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP22ek0109488
Organisme : Japan Society for the Promotion of Science London (JSPS London)
ID : JP23K18273
Organisme : Japan Society for the Promotion of Science London (JSPS London)
ID : JP23H02794
Informations de copyright
© 2024. The Author(s).
Références
Aleck KA, Grix A, Clericuzio C, Kaplan P, Adomian GE, Lachman R, et al. Dyssegmental dysplasias: clinical, radiographic, and morphologic evidence of heterogeneity. Am J Med Genet. 1987;27:295–312.
pubmed: 3605216
doi: 10.1002/ajmg.1320270208
Handmaker SD, Campbell JA, Robinson LD, Chinwah O, Gorlin RJ. Dyssegmental dwarfism: a new syndrome of lethal dwarfism. Birth Defects Orig Artic Ser. 1977;13:79–90.
pubmed: 922143
Rolland JC, Laugier J, Grenier B, Desbuquois G. [Condrodystrophic dwarfism and cleft palate in a newborn]. Ann Pediatr. 1972;19:139–43.
Maldjian C, Chew FS, Klein R, Bonakdarpour A, McCarthy J, Kelly J. Kniest dysplasia: new radiographic features in the skeleton. Radio Case Rep. 2007;2:72–7.
doi: 10.2484/rcr.v2i2.89
Nicole S, Davoine CS, Topaloglu H, Cattolico L, Barral D, Beighton P, et al. Perlecan, the major proteoglycan of basement membranes, is altered in patients with Schwartz-Jampel syndrome (chondrodystrophic myotonia). Nat Genet. 2000;26:480–3.
pubmed: 11101850
doi: 10.1038/82638
Arikawa-Hirasawa E, Wilcox WR, Le AH, Silverman N, Govindraj P, Hassell JR, et al. Dyssegmental dysplasia, Silverman-Handmaker type, is caused by functional null mutations of the perlecan gene. Nat Genet. 2001;27:431–4.
pubmed: 11279527
doi: 10.1038/86941
Stum M, Davoine CS, Vicart S, Guillot-Noel L, Topaloglu H, Carod-Artal FJ, et al. Spectrum of HSPG2 (Perlecan) mutations in patients with Schwartz-Jampel syndrome. Hum Mutat. 2006;27:1082–91.
pubmed: 16927315
doi: 10.1002/humu.20388
Nakazawa Y, Sasaki K, Mitsutake N, Matsuse M, Shimada M, Nardo T, et al. Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair. Nat Genet. 2012;44:586–92.
pubmed: 22466610
doi: 10.1038/ng.2229
Chen S, Zhou Y, Chen Y, Gu J. fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018;34:i884–90.
pubmed: 30423086
pmcid: 6129281
doi: 10.1093/bioinformatics/bty560
Tischler G, Leonard S. biobambam: tools for read pair collation based algorithms on BAM files. Source Code Biol Med. 2014;9:13.
pmcid: 4075596
doi: 10.1186/1751-0473-9-13
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297–303.
pubmed: 20644199
pmcid: 2928508
doi: 10.1101/gr.107524.110
Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38:e164.
pubmed: 20601685
pmcid: 2938201
doi: 10.1093/nar/gkq603
Takeda JI, Nanatsue K, Yamagishi R, Ito M, Haga N, Hirata H, et al. InMeRF: prediction of pathogenicity of missense variants by individual modeling for each amino acid substitution. NAR Genom Bioinform. 2020;2:lqaa038.
pubmed: 33543123
pmcid: 7671370
doi: 10.1093/nargab/lqaa038
Maddirevula S, Alsahli S, Alhabeeb L, Patel N, Alzahrani F, Shamseldin HE, et al. Expanding the phenome and variome of skeletal dysplasia. Genet Med. 2018;20:1609–16.
pubmed: 29620724
doi: 10.1038/gim.2018.50
Yeo G, Burge CB. Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J Comput Biol. 2004;11:377–94.
pubmed: 15285897
doi: 10.1089/1066527041410418
McMichael G, Bainbridge MN, Haan E, Corbett M, Gardner A, Thompson S, et al. Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy. Mol Psychiatry. 2015;20:176–82.
pubmed: 25666757
doi: 10.1038/mp.2014.189
Lavorgna TR, Gressett TE, Chastain WH, Bix GJ. Perlecan: a review of its role in neurologic and musculoskeletal disease. Front Physiol. 2023;14:1189731.
pubmed: 37324385
pmcid: 10267744
doi: 10.3389/fphys.2023.1189731
Costell M, Mann K, Yamada Y, Timpl R. Characterization of recombinant perlecan domain I and its substitution by glycosaminoglycans and oligosaccharides. Eur J Biochem. 1997;243:115–21.
pubmed: 9030729
doi: 10.1111/j.1432-1033.1997.t01-1-00115.x
Dolan M, Horchar T, Rigatti B, Hassell JR. Identification of sites in domain I of perlecan that regulate heparan sulfate synthesis. J Biol Chem. 1997;272:4316–22.
pubmed: 9020150
doi: 10.1074/jbc.272.7.4316
Costell M, Sasaki T, Mann K, Yamada Y, Timpl R. Structural characterization of recombinant domain II of the basement membrane proteoglycan perlecan. FEBS Lett. 1996;396:127–31.
pubmed: 8914972
doi: 10.1016/0014-5793(96)01082-4
Schulze B, Sasaki T, Costell M, Mann K, Timpl R. Structural and cell-adhesive properties of three recombinant fragments derived from perlecan domain III. Matrix Biol. 1996;15:349–57.
pubmed: 8981331
doi: 10.1016/S0945-053X(96)90138-9
Hopf M, Gohring W, Kohfeldt E, Yamada Y, Timpl R. Recombinant domain IV of perlecan binds to nidogens, laminin-nidogen complex, fibronectin, fibulin-2 and heparin. Eur J Biochem. 1999;259:917–25.
pubmed: 10092882
doi: 10.1046/j.1432-1327.1999.00127.x
Arikawa-Hirasawa E, Rossi SG, Rotundo RL, Yamada Y. Absence of acetylcholinesterase at the neuromuscular junctions of perlecan-null mice. Nat Neurosci. 2002;5:119–23.
pubmed: 11802174
doi: 10.1038/nn801
Gubbiotti MA, Neill T, Iozzo RV. A current view of perlecan in physiology and pathology: a mosaic of functions. Matrix Biol. 2017;57-58:285–98.
pubmed: 27613501
doi: 10.1016/j.matbio.2016.09.003
Martinez JR, Dhawan A, Farach-Carson MC. Modular proteoglycan perlecan/HSPG2: mutations, phenotypes, and functions. Genes. 2018;9:556.
pubmed: 30453502
pmcid: 6266596
doi: 10.3390/genes9110556
Hayes AJ, Farrugia BL, Biose IJ, Bix GJ, Melrose J. Perlecan, a multi-functional, cell-instructive, matrix-stabilizing proteoglycan with roles in tissue development has relevance to connective tissue repair and regeneration. Front Cell Dev Biol. 2022;10:856261.
pubmed: 35433700
pmcid: 9010944
doi: 10.3389/fcell.2022.856261
Arikawa-Hirasawa E. Impact of the heparan sulfate proteoglycan perlecan on human disease and health. Am J Physiol Cell Physiol. 2022;322:C1117–22.
pubmed: 35417267
doi: 10.1152/ajpcell.00113.2022
Rieubland C, Jacquemont S, Mittaz L, Osterheld MC, Vial Y, Superti-Furga A, et al. Phenotypic and molecular characterization of a novel case of dyssegmental dysplasia, Silverman-Handmaker type. Eur J Med Genet. 2010;53:294–8.
pubmed: 20542149
doi: 10.1016/j.ejmg.2010.06.005
Ladhani NN, Chitayat D, Nezarati MM, Laureane MC, Keating S, Silver RJ, et al. Dyssegmental dysplasia, Silverman-Handmaker type: prenatal ultrasound findings and molecular analysis. Prenat Diagn. 2013;33:1039–43.
pubmed: 23836246
doi: 10.1002/pd.4193
Basalom S, Trakadis Y, Shear R, Azouz ME, De Bie I. Dyssegmental dysplasia, Silverman-Handmaker type: a challenging antenatal diagnosis in a dizygotic twin pregnancy. Mol Genet Genom Med. 2018;6:452–6.
doi: 10.1002/mgg3.379
Kosaki R, Kubota M, Uehara T, Suzuki H, Takenouchi T, Kosaki K. Consecutive medical exome analysis at a tertiary center: diagnostic and health-economic outcomes. Am J Med Genet A. 2020;182:1601–7.
pubmed: 32369273
doi: 10.1002/ajmg.a.61589
Kircher M, Witten DM, Jain P, O’Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46:310–5.
pubmed: 24487276
pmcid: 3992975
doi: 10.1038/ng.2892
Quang D, Chen Y, Xie X. DANN: a deep learning approach for annotating the pathogenicity of genetic variants. Bioinformatics. 2015;31:761–3.
pubmed: 25338716
doi: 10.1093/bioinformatics/btu703
Arikawa-Hirasawa E, Wilcox WR, Yamada Y. Dyssegmental dysplasia, Silverman-Handmaker type: unexpected role of perlecan in cartilage development. Am J Med Genet. 2001;106:254–7.
pubmed: 11891676
doi: 10.1002/ajmg.10229
Unger S, Ferreira CR, Mortier GR, Ali H, Bertola DR, Calder A, et al. Nosology of genetic skeletal disorders: 2023 revision. Am J Med Genet A. 2023;191:1164–209.
pubmed: 36779427
doi: 10.1002/ajmg.a.63132
Lin PY, Hung JH, Hsu CK, Chang YT, Sun YT. A novel pathogenic HSPG2 mutation in Schwartz-Jampel syndrome. Front Neurol. 2021;12:632336.
pubmed: 33767660
pmcid: 7985266
doi: 10.3389/fneur.2021.632336
Padmanabha H, Suthar R, Sankhyan N, Singhi P. Stiffness, facial dysmorphism, and skeletal abnormalities: Schwartz-Jampel syndrome 1A. J Pediatr. 2018;200:286–286.1.
pubmed: 29866592
doi: 10.1016/j.jpeds.2018.04.077
Bauche S, Boerio D, Davoine CS, Bernard V, Stum M, Bureau C, et al. Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome. Neuromuscul Disord. 2013;23:998–1009.
pubmed: 24011702
doi: 10.1016/j.nmd.2013.07.005
Iwata S, Ito M, Nakata T, Noguchi Y, Okuno T, Ohkawara B, et al. A missense mutation in domain III in HSPG2 in Schwartz-Jampel syndrome compromises secretion of perlecan into the extracellular space. Neuromuscul Disord. 2015;25:667–71.
pubmed: 26031903
doi: 10.1016/j.nmd.2015.05.002
Brugnoni R, Marelli D, Iacomino N, Canioni E, Cappelletti C, Maggi L, et al. Novel HSPG2 gene mutation causing Schwartz–Jampel syndrome in a Moroccan family: a literature review. Genes. 2023;14:1753.
pubmed: 37761893
pmcid: 10531088
doi: 10.3390/genes14091753
Das Bhowmik A, Dalal A, Matta D, Kandadai RM, Kanikannan MA, Aggarwal S. Identification of a novel splice site HSPG2 mutation and prenatal diagnosis in Schwartz Jampel syndrome type 1 using whole exome sequencing. Neuromuscul Disord. 2016;26:809–14.
pubmed: 27521129
doi: 10.1016/j.nmd.2016.07.004
Dai L, Fang F, Huang Y, Cheng H, Ren C. [Clinical and genetic features of Schwartz-Jampel syndrome in a Chinese child: case report and literature review]. Zhonghua Er Ke Za Zhi. 2015;53:855–9.
pubmed: 26758326
Arikawa-Hirasawa E, Le AH, Nishino I, Nonaka I, Ho NC, Francomano CA, et al. Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia. Am J Hum Genet. 2002;70:1368–75.
pubmed: 11941538
pmcid: 447613
doi: 10.1086/340390
Yan W, Dai J, Shi D, Xu X, Han X, Xu Z, et al. Novel HSPG2 mutations causing Schwartz‑Jampel syndrome type 1 in a Chinese family: a case report. Mol Med Rep. 2018;18:1761–5.
pubmed: 29901129
Maini I, Farnetti E, Nicoli D, Pavlidis E, Spagnoli C, Salerno GG, et al. Co-occurrence of an HSPG2 Missense variant and functional polymorphisms in atypical Schwartz–Jampel syndrome type 1 with obesity: a case report. J Pediatr Neurol. 2019;17:149–52.
doi: 10.1055/s-0038-1668163