Araştırma Makalesi
BibTex RIS Kaynak Göster

A very rare disease of lymphatic malformation 6: five new patients and review of the literatur

Yıl 2023, Cilt: 10 Sayı: 2, 71 - 75, 30.06.2023
https://doi.org/10.34087/cbusbed.1224826

Öz

Objective: Lymphatic Malformation 6 (MIM no:616843) is characterized by generalized edema, bilateral pleural effusions, ascites and non-immune hydrops fetalis. PIEZO1 gene has been associated with the LMPHM6 disorder. Here, we aimed to evaluate five patients from two different families, with various clinical presentations of generalized lymphatic dysplasia.
Materials and Methods: Between January 2015 and January 2021, 5 cases with were evaluated with a pre-diagnosis of congenital lymphatic malformation. Whole exome sequencing was performed on the probands, and family segregation analysis was performed by Sanger sequencing.
Results: We identified a novel compound heterozygous PIEZO1 gene: NM_001142864.4: c.4030_4032delGAG (E1344del)/ c.5455_5456delAA (K1819Efs*46) variants in the first family and a novel homozygous PIEZO1 gene: c.5876A>G (D1959G) variant in the second family.
Conclusion: This study, which presents the clinical features and variations of five patients with long-term follow-up, contributed to the phenotypic and mutation spectrum of Lymphatic Malformation 6. The novel compound heterozygous E1344del/K1819Efs*46 variation leads to a premature stop codon that caused a shorter protein product. It was thought that two compound nonsense variations might be associated with the poor prognosis of family 1. Also, the second novel c.5876A>G (D1959G) biallelic homozygous mutation was thought to be associated with impaired PIEZO1 by causing loss of function. This study was the first LMPHM6 report from the Turkish population.
Keywords: Neurofibromatosis type 1, Next generation DNA sequencing, NF1 gene, novel variants

Teşekkür

All individuals participating in the study were informed about the study and an informed consent form was obtained. We thank all the individuals who took part in this study.

Kaynakça

  • Lukacs, V, Mathu, J, et al. Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia. Nature comminications, 2015, 6, 8329.
  • Andolfo, I, De Rosa, G, et al., PIEZO1 hypomorphic variants in congenital lymphatic dysplasia cause shape and hydration alterations of red blood cells, Frontiers in physiology, 2019, 10, 258.
  • Fotiou, E, Martin-Almedina, S, et al., Author Correction: Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis, Nature communications, 2019, 10, 1951.
  • Andolfo, I, Alper, S.L, et al., Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1, Blood, 2013, 121, 3925-3935.
  • Richards, S, Aziz N, et al., ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genetics in Medicine, 2015, 17, 405-24.
  • Datkhaeva, I, Arboleda, V.A, et al., Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis, American Journal of Medical Genetics Part A, 2018, 176, 2829-2834.
  • Yates, C.L, Monaghan, .KG, et al., Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development, Genetics in Medicine, 2017, 19, 1171-1178.
  • Lukacs, V, Mathur, J, et al., Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia, Nature comminications, 2015, 6, 8329.
  • Andolfo, I, De Rosa, G, et al. PIEZO1 hypomorphic variants in congenital lymphatic dysplasia cause shape and hydration alterations of red blood cells, Frontiers in physiology, 2019, 10, 258.
  • Fotiou, E, Martin-Almedina, S, et al. Author Correction: Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis, Nature communications, 2019, 10, 1951.
  • Andolfo, I, Alper S.L, et al., Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1, Blood, 2013, 121, 3925-3935.
  • Richards, S, Aziz, N, et al., ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genetics in Medicine, 2015, 17, 405-24.
  • Datkhaeva, I, Arboleda, V.A, et al., Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis, American Journal of Medical Genetics Part A, 2018, 176, 2829-2834.
  • Yates, C.L, Monaghan, K.G, et al., Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development, Genetics in Medicine, 2017, 19, 1171-1178.
  • Vora, N.L, Powell, B, et al., Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges, Genetics in Medicine, 2017, 19, 1207-1216.
  • Shamseldin, H.E, Kurdi, W, et al., Molecular autopsy in maternal–fetal medicine, Genetics in Medicine, 2018, 20, 420-427.
  • Sparks, T.N, Lianoglou, B.R, et al., Exome sequencing for prenatal diagnosis in nonimmune hydrops fetalis, New England Journal of Medicine, 2020, 383, 1746-1756.
  • Guo, W, Lai, Y, et al., Trio‐whole‐exome sequencing and preimplantation genetic diagnosis for unexplained recurrent fetal malformations, Human mutation, 2020, 41, 432-448.
  • Lukacs, V, Mathur, J, et al., Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia, Nature comminications, 2015, 6, 8329.
  • Andolfo, I, De Rosa, G, et al. PIEZO1 hypomorphic variants in congenital lymphatic dysplasia cause shape and hydration alterations of red blood cells, Frontiers in physiology, 2019, 10, 258.
  • Fotiou,, E, Martin-Almedina S, et al. Author Correction: Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis, Nature communications, 2019,10, 1951.
  • Andolfo, I, Alper, S.L, et al., Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1, Blood, 2013, 121, 3925-3935.
  • Richards, S, Aziz, N, et al., ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genetics in Medicine, 2015, 17, 405-24.
  • Datkhaeva, I, Arboleda, V.A, et al., Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis, American Journal of Medical Genetics Part A, 2018, 176, 2829-2834.
  • Yates, C.L, Monaghan, K.G, et al., Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development, Genetics in Medicine, 2017, 19, 1171-1178.
  • Vora, N.L, Powell, B, et al., Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges, Genetics in Medicine, 2017, 19, 1207-1216.
  • Shamseldin, H.E, Kurdi, W, et al., Molecular autopsy in maternal–fetal medicine, Genetics in Medicine, 2018, 20, 420-427.
  • Sparks, T.N, Lianoglou, B.R, et al., Exome sequencing for prenatal diagnosis in nonimmune hydrops fetalis, New England Journal of Medicine, 2020, 383, 1746-1756.
  • Guo, W, Lai, Y, et al., Trio‐whole‐exome sequencing and preimplantation genetic diagnosis for unexplained recurrent fetal malformations, Human mutation, 2020, 41, 432-448.
  • Chen, Y, Jiang, Y, Chen, B, Qian, Y, Liu, J, Yang, M, et al., Case Report: Whole Exome Sequencing Revealed Two Novel Mutations of PIEZO1 Implicated in Nonimmune Hydrops Fetalis, Frontiers in genetics, 2021, 12, 684555.
  • Venselaar, H, Te Beek, T.A.H, et al., Protein structure analysis of mutations causing inheritable diseases, An e-Science approach with life scientist friendly interfaces, BMC Bioinformatics, 2010, 11, 548.

A very rare disease of lymphatic malformation 6: two novel PIEZO1 variants and review of the literature

Yıl 2023, Cilt: 10 Sayı: 2, 71 - 75, 30.06.2023
https://doi.org/10.34087/cbusbed.1224826

Öz

Objective: Lymphatic Malformation 6 (MIM no:616843) is characterized by generalized edema, bilateral pleural effusion, ascites and non-immune hydrops fetalis. PIEZO1 gene has been associated with the this disorder. Here, we aimed to evaluate cases with various clinical presentations of generalized lymphatic dysplasia.
Materials and Methods: Between January 2015 and January 2021, 5 cases with were evaluated with a pre-diagnosis of generalized lymphatic dysplasia. Whole exome sequencing was performed on the probands, and family segregation analysis was performed by Sanger sequencing.
Results: We identified a novel compound heterozygous PIEZO1 gene: NM_001142864.4: c.4030_4032delGAG (E1344del)/ c.5455_5456delAA (K1819Efs*46) variants in the first family and a novel homozygous PIEZO1 gene: c.5876A>G (D1959G) variant in the second family.
Conclusion: This study, which presents the clinical features and variations of five cases with long-term follow-up, contributed to the phenotypic and mutation spectrum a very rare disease of Lymphatic Malformation 6. The novel compound heterozygous E1344del/K1819Efs*46 variation leads to a premature stop codon that caused a shorter PIEZO1 protein product. It was thought that two compound nonsense variations might be associated with the poor prognosis of family 1. Also, the second novel c.5876A>G (D1959G) homozygous mutation was thought to be associated with impaired PIEZO1 by causing loss of function. Also, this study was the first LMPHM6 report from the Turkish population.

Kaynakça

  • Lukacs, V, Mathu, J, et al. Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia. Nature comminications, 2015, 6, 8329.
  • Andolfo, I, De Rosa, G, et al., PIEZO1 hypomorphic variants in congenital lymphatic dysplasia cause shape and hydration alterations of red blood cells, Frontiers in physiology, 2019, 10, 258.
  • Fotiou, E, Martin-Almedina, S, et al., Author Correction: Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis, Nature communications, 2019, 10, 1951.
  • Andolfo, I, Alper, S.L, et al., Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1, Blood, 2013, 121, 3925-3935.
  • Richards, S, Aziz N, et al., ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genetics in Medicine, 2015, 17, 405-24.
  • Datkhaeva, I, Arboleda, V.A, et al., Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis, American Journal of Medical Genetics Part A, 2018, 176, 2829-2834.
  • Yates, C.L, Monaghan, .KG, et al., Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development, Genetics in Medicine, 2017, 19, 1171-1178.
  • Lukacs, V, Mathur, J, et al., Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia, Nature comminications, 2015, 6, 8329.
  • Andolfo, I, De Rosa, G, et al. PIEZO1 hypomorphic variants in congenital lymphatic dysplasia cause shape and hydration alterations of red blood cells, Frontiers in physiology, 2019, 10, 258.
  • Fotiou, E, Martin-Almedina, S, et al. Author Correction: Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis, Nature communications, 2019, 10, 1951.
  • Andolfo, I, Alper S.L, et al., Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1, Blood, 2013, 121, 3925-3935.
  • Richards, S, Aziz, N, et al., ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genetics in Medicine, 2015, 17, 405-24.
  • Datkhaeva, I, Arboleda, V.A, et al., Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis, American Journal of Medical Genetics Part A, 2018, 176, 2829-2834.
  • Yates, C.L, Monaghan, K.G, et al., Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development, Genetics in Medicine, 2017, 19, 1171-1178.
  • Vora, N.L, Powell, B, et al., Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges, Genetics in Medicine, 2017, 19, 1207-1216.
  • Shamseldin, H.E, Kurdi, W, et al., Molecular autopsy in maternal–fetal medicine, Genetics in Medicine, 2018, 20, 420-427.
  • Sparks, T.N, Lianoglou, B.R, et al., Exome sequencing for prenatal diagnosis in nonimmune hydrops fetalis, New England Journal of Medicine, 2020, 383, 1746-1756.
  • Guo, W, Lai, Y, et al., Trio‐whole‐exome sequencing and preimplantation genetic diagnosis for unexplained recurrent fetal malformations, Human mutation, 2020, 41, 432-448.
  • Lukacs, V, Mathur, J, et al., Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia, Nature comminications, 2015, 6, 8329.
  • Andolfo, I, De Rosa, G, et al. PIEZO1 hypomorphic variants in congenital lymphatic dysplasia cause shape and hydration alterations of red blood cells, Frontiers in physiology, 2019, 10, 258.
  • Fotiou,, E, Martin-Almedina S, et al. Author Correction: Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis, Nature communications, 2019,10, 1951.
  • Andolfo, I, Alper, S.L, et al., Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1, Blood, 2013, 121, 3925-3935.
  • Richards, S, Aziz, N, et al., ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genetics in Medicine, 2015, 17, 405-24.
  • Datkhaeva, I, Arboleda, V.A, et al., Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis, American Journal of Medical Genetics Part A, 2018, 176, 2829-2834.
  • Yates, C.L, Monaghan, K.G, et al., Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development, Genetics in Medicine, 2017, 19, 1171-1178.
  • Vora, N.L, Powell, B, et al., Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges, Genetics in Medicine, 2017, 19, 1207-1216.
  • Shamseldin, H.E, Kurdi, W, et al., Molecular autopsy in maternal–fetal medicine, Genetics in Medicine, 2018, 20, 420-427.
  • Sparks, T.N, Lianoglou, B.R, et al., Exome sequencing for prenatal diagnosis in nonimmune hydrops fetalis, New England Journal of Medicine, 2020, 383, 1746-1756.
  • Guo, W, Lai, Y, et al., Trio‐whole‐exome sequencing and preimplantation genetic diagnosis for unexplained recurrent fetal malformations, Human mutation, 2020, 41, 432-448.
  • Chen, Y, Jiang, Y, Chen, B, Qian, Y, Liu, J, Yang, M, et al., Case Report: Whole Exome Sequencing Revealed Two Novel Mutations of PIEZO1 Implicated in Nonimmune Hydrops Fetalis, Frontiers in genetics, 2021, 12, 684555.
  • Venselaar, H, Te Beek, T.A.H, et al., Protein structure analysis of mutations causing inheritable diseases, An e-Science approach with life scientist friendly interfaces, BMC Bioinformatics, 2010, 11, 548.
Toplam 31 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Kadın Hastalıkları ve Doğum
Bölüm Araştırma Makalesi
Yazarlar

Hamıde Betul Gerik Celebi 0000-0001-5218-7880

Murat Akbas 0000-0001-5036-437X

Tuncay Yüce 0000-0002-7085-5878

Serdar Ceylaner 0000-0003-2786-1911

Sırrı Çam 0000-0002-0972-8896

Yayımlanma Tarihi 30 Haziran 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 10 Sayı: 2

Kaynak Göster

APA Gerik Celebi, H. B., Akbas, M., Yüce, T., Ceylaner, S., vd. (2023). A very rare disease of lymphatic malformation 6: five new patients and review of the literatur. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 10(2), 71-75. https://doi.org/10.34087/cbusbed.1224826
AMA Gerik Celebi HB, Akbas M, Yüce T, Ceylaner S, Çam S. A very rare disease of lymphatic malformation 6: five new patients and review of the literatur. CBU-SBED. Haziran 2023;10(2):71-75. doi:10.34087/cbusbed.1224826
Chicago Gerik Celebi, Hamıde Betul, Murat Akbas, Tuncay Yüce, Serdar Ceylaner, ve Sırrı Çam. “A Very Rare Disease of Lymphatic Malformation 6: Five New Patients and Review of the Literatur”. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 10, sy. 2 (Haziran 2023): 71-75. https://doi.org/10.34087/cbusbed.1224826.
EndNote Gerik Celebi HB, Akbas M, Yüce T, Ceylaner S, Çam S (01 Haziran 2023) A very rare disease of lymphatic malformation 6: five new patients and review of the literatur. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 10 2 71–75.
IEEE H. B. Gerik Celebi, M. Akbas, T. Yüce, S. Ceylaner, ve S. Çam, “A very rare disease of lymphatic malformation 6: five new patients and review of the literatur”, CBU-SBED, c. 10, sy. 2, ss. 71–75, 2023, doi: 10.34087/cbusbed.1224826.
ISNAD Gerik Celebi, Hamıde Betul vd. “A Very Rare Disease of Lymphatic Malformation 6: Five New Patients and Review of the Literatur”. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 10/2 (Haziran 2023), 71-75. https://doi.org/10.34087/cbusbed.1224826.
JAMA Gerik Celebi HB, Akbas M, Yüce T, Ceylaner S, Çam S. A very rare disease of lymphatic malformation 6: five new patients and review of the literatur. CBU-SBED. 2023;10:71–75.
MLA Gerik Celebi, Hamıde Betul vd. “A Very Rare Disease of Lymphatic Malformation 6: Five New Patients and Review of the Literatur”. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, c. 10, sy. 2, 2023, ss. 71-75, doi:10.34087/cbusbed.1224826.
Vancouver Gerik Celebi HB, Akbas M, Yüce T, Ceylaner S, Çam S. A very rare disease of lymphatic malformation 6: five new patients and review of the literatur. CBU-SBED. 2023;10(2):71-5.