Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism

Francesca Clementina Radio; Lavinia Di Meglio; Emanuele Agolini; Emanuele Bellacchio; Martina Rinelli; Paolo Toscano; Renata Boldrini; Antonio Novelli; Aniello Di Meglio; Bruno Dallapiccola

doi:10.1002/mgg3.376

Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism

Francesca Clementina Radio, Lavinia Di Meglio, Emanuele Agolini, Emanuele Bellacchio, Martina Rinelli, Paolo Toscano, Renata Boldrini, Antonio Novelli, Aniello Di Meglio, Bruno Dallapiccola

Ospedale Pediatrico Bambino Gesu

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly-hydrocephaly and multiple pterygium due to fetal akinesia. To date, around 45 cases from 27 families have been reported, and the pathogenic bi-allelic mutations in FLVCR2 gene described in 15 families. The pathogenesis of this condition has not been fully elucidated so far.

METHODS: We report on an additional family with two affected fetuses carrying a novel homozygous mutation in FLVCR2 gene, and describe the impact of known mutants on the protein structural and functional impairment.

RESULTS: The present report confirms the genetic homogeneity of Fowler syndrome and describes a new FLVCR2 mutation affecting the protein function. The structural analysis of the present and previously published FLVCR2 mutations supports the hypothesis of a reduced heme import as the underlying disease's mechanism due to the stabilization of the occluded conformation or a protein misfolding.

CONCLUSION: Our data suggest the hypothesis of heme deficiency as the major pathogenic mechanism of Fowler syndrome.

Original language	English
Pages (from-to)	446-451
Number of pages	6
Journal	Molecular genetics & genomic medicine
Volume	6
Issue number	3
DOIs	https://doi.org/10.1002/mgg3.376
Publication status	Published - May 2018

Keywords

Alleles
Amino Acid Sequence/genetics
Fetus/pathology
Heme/genetics
Humans
Hydranencephaly/genetics
Hydrocephalus/genetics
Membrane Transport Proteins/genetics
Mutation
Receptors, Virus/genetics
Vascular Diseases/genetics

Access to Document

10.1002/mgg3.376

Fingerprint Dive into the research topics of 'Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism'. Together they form a unique fingerprint.

Cite this

Radio, F. C., Di Meglio, L., Agolini, E., Bellacchio, E., Rinelli, M., Toscano, P., Boldrini, R., Novelli, A., Di Meglio, A., & Dallapiccola, B. (2018). Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism. Molecular genetics & genomic medicine, 6(3), 446-451. https://doi.org/10.1002/mgg3.376

Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome : Report of a family and insight into the disease's mechanism. / Radio, Francesca Clementina; Di Meglio, Lavinia; Agolini, Emanuele; Bellacchio, Emanuele; Rinelli, Martina; Toscano, Paolo; Boldrini, Renata; Novelli, Antonio; Di Meglio, Aniello; Dallapiccola, Bruno.

In: Molecular genetics & genomic medicine, Vol. 6, No. 3, 05.2018, p. 446-451.

Research output: Contribution to journal › Article › peer-review

Radio, FC, Di Meglio, L, Agolini, E, Bellacchio, E, Rinelli, M, Toscano, P, Boldrini, R, Novelli, A, Di Meglio, A & Dallapiccola, B 2018, 'Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism', Molecular genetics & genomic medicine, vol. 6, no. 3, pp. 446-451. https://doi.org/10.1002/mgg3.376

Radio, Francesca Clementina ; Di Meglio, Lavinia ; Agolini, Emanuele ; Bellacchio, Emanuele ; Rinelli, Martina ; Toscano, Paolo ; Boldrini, Renata ; Novelli, Antonio ; Di Meglio, Aniello ; Dallapiccola, Bruno. / Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome : Report of a family and insight into the disease's mechanism. In: Molecular genetics & genomic medicine. 2018 ; Vol. 6, No. 3. pp. 446-451.

@article{b71323c876654cd9adb793be23c113f9,

title = "Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism",

abstract = "BACKGROUND: Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly-hydrocephaly and multiple pterygium due to fetal akinesia. To date, around 45 cases from 27 families have been reported, and the pathogenic bi-allelic mutations in FLVCR2 gene described in 15 families. The pathogenesis of this condition has not been fully elucidated so far.METHODS: We report on an additional family with two affected fetuses carrying a novel homozygous mutation in FLVCR2 gene, and describe the impact of known mutants on the protein structural and functional impairment.RESULTS: The present report confirms the genetic homogeneity of Fowler syndrome and describes a new FLVCR2 mutation affecting the protein function. The structural analysis of the present and previously published FLVCR2 mutations supports the hypothesis of a reduced heme import as the underlying disease's mechanism due to the stabilization of the occluded conformation or a protein misfolding.CONCLUSION: Our data suggest the hypothesis of heme deficiency as the major pathogenic mechanism of Fowler syndrome.",

keywords = "Alleles, Amino Acid Sequence/genetics, Fetus/pathology, Heme/genetics, Humans, Hydranencephaly/genetics, Hydrocephalus/genetics, Membrane Transport Proteins/genetics, Mutation, Receptors, Virus/genetics, Vascular Diseases/genetics",

author = "Radio, {Francesca Clementina} and {Di Meglio}, Lavinia and Emanuele Agolini and Emanuele Bellacchio and Martina Rinelli and Paolo Toscano and Renata Boldrini and Antonio Novelli and {Di Meglio}, Aniello and Bruno Dallapiccola",

note = "{\textcopyright} 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.",

year = "2018",

month = may,

doi = "10.1002/mgg3.376",

language = "English",

volume = "6",

pages = "446--451",

journal = "Molecular genetics & genomic medicine",

issn = "2324-9269",

publisher = "John Wiley and Sons Inc.",

number = "3",

}

TY - JOUR

T1 - Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome

T2 - Report of a family and insight into the disease's mechanism

AU - Radio, Francesca Clementina

AU - Di Meglio, Lavinia

AU - Agolini, Emanuele

AU - Bellacchio, Emanuele

AU - Rinelli, Martina

AU - Toscano, Paolo

AU - Boldrini, Renata

AU - Novelli, Antonio

AU - Di Meglio, Aniello

AU - Dallapiccola, Bruno

PY - 2018/5

Y1 - 2018/5

N2 - BACKGROUND: Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly-hydrocephaly and multiple pterygium due to fetal akinesia. To date, around 45 cases from 27 families have been reported, and the pathogenic bi-allelic mutations in FLVCR2 gene described in 15 families. The pathogenesis of this condition has not been fully elucidated so far.METHODS: We report on an additional family with two affected fetuses carrying a novel homozygous mutation in FLVCR2 gene, and describe the impact of known mutants on the protein structural and functional impairment.RESULTS: The present report confirms the genetic homogeneity of Fowler syndrome and describes a new FLVCR2 mutation affecting the protein function. The structural analysis of the present and previously published FLVCR2 mutations supports the hypothesis of a reduced heme import as the underlying disease's mechanism due to the stabilization of the occluded conformation or a protein misfolding.CONCLUSION: Our data suggest the hypothesis of heme deficiency as the major pathogenic mechanism of Fowler syndrome.

AB - BACKGROUND: Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly-hydrocephaly and multiple pterygium due to fetal akinesia. To date, around 45 cases from 27 families have been reported, and the pathogenic bi-allelic mutations in FLVCR2 gene described in 15 families. The pathogenesis of this condition has not been fully elucidated so far.METHODS: We report on an additional family with two affected fetuses carrying a novel homozygous mutation in FLVCR2 gene, and describe the impact of known mutants on the protein structural and functional impairment.RESULTS: The present report confirms the genetic homogeneity of Fowler syndrome and describes a new FLVCR2 mutation affecting the protein function. The structural analysis of the present and previously published FLVCR2 mutations supports the hypothesis of a reduced heme import as the underlying disease's mechanism due to the stabilization of the occluded conformation or a protein misfolding.CONCLUSION: Our data suggest the hypothesis of heme deficiency as the major pathogenic mechanism of Fowler syndrome.

KW - Alleles

KW - Amino Acid Sequence/genetics

KW - Fetus/pathology

KW - Heme/genetics

KW - Humans

KW - Hydranencephaly/genetics

KW - Hydrocephalus/genetics

KW - Membrane Transport Proteins/genetics

KW - Mutation

KW - Receptors, Virus/genetics

KW - Vascular Diseases/genetics

U2 - 10.1002/mgg3.376

DO - 10.1002/mgg3.376

M3 - Article

C2 - 29500860

VL - 6

SP - 446

EP - 451

JO - Molecular genetics & genomic medicine

JF - Molecular genetics & genomic medicine

SN - 2324-9269

IS - 3

ER -