Prenatal diagnosis of a nonsense mutation in the L1CAM gene resulting in congenital hydrocephalus: A case report and literature review

Wang,Rongyue; Chen,Hua; Wang,Xiaona; Huang,Shiyuan; Xie,Ailan; Wu,Xinmei

doi:10.3892/etm.2021.10807

Prenatal diagnosis of a nonsense mutation in the L1CAM gene resulting in congenital hydrocephalus: A case report and literature review

Authors:
- Rongyue Wang
- Hua Chen
- Xiaona Wang
- Shiyuan Huang
- Ailan Xie
- Xinmei Wu
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China, Department of Rehabilitation, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China, Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China
Published online on: October 8, 2021 https://doi.org/10.3892/etm.2021.10807
Article Number: 1416
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Congenital hydrocephalus is frequently caused by mutations in the L1 cell adhesion molecule (L1CAM) gene. The purpose of the present study was to identify possible causes of fetal hydrocephalus in a Chinese family. The samples from the parents and the hydrocephalic fetus were collected. Whole‑exome sequencing and in‑depth mutation analysis were performed. The identified variant, c.1267C>T.(p.Q423X), is situated on exon 11 of L1CAM gene (chromosome X:153134975). The fetus was confirmed to be hemizygous for the nonsense mutation and the mother was a heterozygous carrier. The mutation turns a glutamine into a premature stop codon at amino acid position 423. In conclusion, in the present study, a nonsense mutation in the L1CAM gene was identified during the prenatal diagnosis of a congenital hydrocephalic fetus from a Chinese family. The diagnosis highlighted the necessity of genetic screening for prenatal diagnosis.

View Figures

View References

1	Moos M, Tacke R, Scherer H, Teplow D, Früh K and Schachner M: Neural adhesion molecule L1 as a member of the immunoglobulinsuperfamily with binding domains similar to fibronectin. Nature. 334:701–703. 1988.PubMed/NCBI View Article : Google Scholar
2	Basel-Vanagaite L, Straussberg R, Friez MJ, Inbar D, Korenreich L, Shohat M and Schwartz CE: Expanding the phenotypic spectrum of L1CAM-associated disease. Clin Genet. 69:414–419. 2006.PubMed/NCBI View Article : Google Scholar
3	Patzke C, Acuna C, Giam LR, Wernig M and Sudhof TC: Conditional deletion of L1CAM in human neurons impairs both axonal and dendritic arborization and action potential generation. J Exp Med. 213:499–515. 2016.PubMed/NCBI View Article : Google Scholar
4	Chang S, Rathjen FG and Raper JA: Extension of neuritis on axons is impaired by antibodies against specific neural cell surface glycoproteins. J Cell Biol. 104:355–362. 1987.PubMed/NCBI View Article : Google Scholar
5	Rathjen FG and Schachner M: Immunocytological and biochemical characterization of a new neuronal cell surface component (L1 antigen) which is involved in cell adhesion. EMBO J. 3:1–10. 1984.PubMed/NCBI
6	Ferese R, Zampatti S, Griguoli AMP, Fornai F, Giardina E, Barrano G, Albano V, Campopiano R, Scala S, Novelli G and Gambardella S: A new splicing mutation in the L1CAM gene responsible for X-linked hydrocephalus (HSAS). J Mol Neurosci. 59:376–381. 2016.PubMed/NCBI View Article : Google Scholar
7	Finckh U, Schröder J, Ressler B, Veske A and Gal A: Spectrum and detection rate of L1CAM mutations in isolated and familial cases with clinically suspected L1-disease. Am J Med Genet. 92:40–46. 2000.PubMed/NCBI View Article : Google Scholar
8	Okamoto N, Del Maestro R, Valero R, Monros E, Poo P, Kanemura Y and Yamasaki M: Hydrocephalus and Hirschsprung's disease with a mutation of L1CAM. J Hum Genet. 49:334–337. 2004.PubMed/NCBI View Article : Google Scholar
9	Fransen E, Van Camp G, D'Hooge R, Vits L and Willems PJ: Genotype-phenotype correlation in L1 associated diseases. J Med Genet. 35:399–404. 1998.PubMed/NCBI View Article : Google Scholar
10	Vos YJ, de Walle HE, Bos KK, Stegeman JA, Ten Berge AM, Bruining M, van Maarle MC, Elting MW, den Hollander NS, Hamel B, et al: Genotype-phenotype correlationsin L1 syndrome: A guide for genetic counselling and mutation analysis. J Med Genet. 47:169–175. 2010.PubMed/NCBI View Article : Google Scholar
11	Yamasaki M, Thompson P and Lemmon V: CRASH syndrome: Mutations in L1CAM correlate with severity of the disease. Neuropediatrics. 28:175–178. 1997.PubMed/NCBI View Article : Google Scholar
12	Rekate HL: The definition and classification of hydrocephalus: A personal recommendation to stimulate debate. Cerebrospinal Fluid Res. 5(2)2008.PubMed/NCBI View Article : Google Scholar
13	Vos YJ and Hofstra RM: An updated and upgraded L1CAM mutation database. Hum Mutat. 31:E1102–E1109. 2010.PubMed/NCBI View Article : Google Scholar
14	Schrander-Stumpel C and Fryns JP: Congenital hydrocephalus: Nosology and guidelines for clinical approach and genetic counselling. Eur J Pediatr. 157:355–362. 1998.PubMed/NCBI View Article : Google Scholar
15	Noronha TR, Rohr SS and Chauffaille MLLF: Identifying the similarities and differences between single nucleotide polymorphism array (SNPa) analysis and karyotyping in acute myeloid leukemia and myelodysplastic syndromes. Rev Bras Hematol Hemoter. 37:48–54. 2015.PubMed/NCBI View Article : Google Scholar
16	Guo D, Shi Y, Jian W, Fu Y, Yang H, Guo M, Yong W, Chen G, Deng H, Qin Y, et al: A novel nonsense mutation in the L1CAM gene responsible for X-linked congenital hydrocephalus. J Gene Med. 22(e3180)2020.PubMed/NCBI View Article : Google Scholar
17	Kong W, Wang X, Zhao J, Kang M, Xi N and Li S: A new frameshift mutation in L1CAM producing X-linked hydrocephalus. Mol Genet Genomic Med. 8(e1031)2019.PubMed/NCBI View Article : Google Scholar
18	Ochando I, Vidal V, Gascón J, Acién M, Urbano A and Rueda J: Prenatal diagnosis of X-linked hydrocephalus in a family with a novel mutation in L1CAM gene. J Obstet Gynaecol. 36:403–405. 2016.PubMed/NCBI View Article : Google Scholar
19	Isik E, Onay H, Atik T, Akgun B, Cogulu O and Ozkinay F: Clinical and genetic features of L1 syndrome patients: Definition of two novel mutations. Clin Neurol Neurosurg. 172:20–23. 2018.PubMed/NCBI View Article : Google Scholar
20	Vinci M, Falco M, Castiglia L, Grillo L, Spalletta A, Sturnio M, Galesi O, Salemi M, Gloria A, Amata S, et al: Identification of novel mutations in L1CAM gene by a DHPLC-based assay. Genes Genomics. 38:1159–1164. 2016.
21	Gu SM, Orth U, Vske A, Enders H, Klunder K, Schlosser M, Engel W, Schwinger E and Gal A: Five novel mutations in the L1CAM gene in families with X linked hydrocephalus. J Med Genet. 33:103–106. 1996.PubMed/NCBI View Article : Google Scholar
22	Gu SM, Orth U, Zankl M, Schröder J and Gal A: Molecular analysis of the L1CAM gene in patients with X-linked hydrocephalus demonstrates eight novel mutations and suggests non-allelic heterogeneity of the trait. Am J Med Genet. 71:336–340. 1997.PubMed/NCBI View Article : Google Scholar
23	Kanemura Y, Okamoto N, Sakamoto H, Shofuda T, Kamiguchi H and Yamasaki M: Molecular mechanisms and neuroimaging criteria for severe L1 syndrome with X-linked hydrocephalus. J Neurosurg. 105 (Suppl 5):S403–S412. 2006.PubMed/NCBI View Article : Google Scholar
24	Jackson SR, Guner YS, Woo R, Randolph LM, Ford H and Shin CE: L1CAM mutation in association with X-linked hydrocephalus and Hirschsprung's disease. Pediatr Surg Int. 25:823–825. 2009.PubMed/NCBI View Article : Google Scholar
25	Takenouchi T, Nakazawa M, Kanemura Y, Shimozato S, Yamasaki M, Takahashi T and Kosaki K: Hydrocephalus with Hirschsprung disease: Severe end of X-linked hydrocephalus spectrum. Am J Med Genet A. 158:812–815. 2012.PubMed/NCBI View Article : Google Scholar
26	Adle-Biassette H, Saugier-Veber P, Fallet-Bianco C, Delezoide AL, Razavi F, Drouot N, Bazin A, Beaufrère AM, Bessières B, Blesson S, et al: Neuropathological review of 138 cases genetically tested for X-linked hydrocephalus: Evidence for closely related clinical entities of unknown molecular bases. Acta Neuropathol. 126:427–442. 2013.PubMed/NCBI View Article : Google Scholar
27	Marín R, Ley-Martos M, Gutiérrez G, Rodríguez-Sánchez F, Arroyo D and Mora-López F: Three cases with L1 syndrome and two novel mutations in the L1CAM gene. Eur J Pediatr. 174:1541–1544. 2015.PubMed/NCBI View Article : Google Scholar
28	Kumar P, Henikoff S and Ng PC: Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 4:1073–1081. 2009.PubMed/NCBI View Article : Google Scholar
29	Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS and Sunyaev SR: A method and server for predicting damaging missense mutations. Nat Methods. 7:248–249. 2010.PubMed/NCBI View Article : Google Scholar
30	Peiro JL and Fabbro MD: Fetal therapy for congenital hydrocephalus-where we came from and where we are going. Childs Nerv Syst. 36:1697–1712. 2020.PubMed/NCBI View Article : Google Scholar
31	Manning FA, Harrison MR and Rodeck C: Catheter shunts for fetal hydronephrosis and hydrocephalus. Report of the international fetal surgery registry. N Engl J Med. 315:336–340. 1986.PubMed/NCBI View Article : Google Scholar
32	Litwinska M, Litwinska E, Czaj M, Polis B, Polis L and Szaflik K: Ventriculo-amniotic shunting for severe fetal ventriculomegaly. Acta Obstet Gynecol Scand. 98:1172–1177. 2019.PubMed/NCBI View Article : Google Scholar
33	Serikawa T, Nishiyama K, Tohyama J, Tazawa R, Goto K, Kuriyama Y, Haino K, Kanemura Y, Yamasaki M, Nakata K, et al: Prenatal molecular diagnosis of X-linked hydrocephalus via a silent C924T mutation in the L1CAM gene. Congenit Anom (Kyoto). 54:243–245. 2014.PubMed/NCBI View Article : Google Scholar
34	Weller S and Gärtner J: Genetic and clinical aspects of X-linked hydrocephalus (L1 disease): Mutations in the L1CAM gene. Hum Mutat. 18:1–12. 2001.PubMed/NCBI View Article : Google Scholar