FLNA mutations in surviving males presenting with connective tissue findings

Two new case reports and review of the literature

Elyssa Cannaerts, Anju Shukla, Mensuda Hasanhodzic, Maaike Alaerts, Dorien Schepers, Lut Van Laer, Katta M. Girisha, Iva Hojsak, Bart Loeys, Aline Verstraeten

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Mutations in the X-linked gene filamin A (FLNA), encoding the actin-binding protein FLNA, cause a wide spectrum of connective tissue, skeletal, cardiovascular and/or gastrointestinal manifestations. Males are typically more severely affected than females with common pre- or perinatal death. Case presentation: We provide a genotype- and phenotype-oriented literature overview of FLNA hemizygous mutations and report on two live-born male FLNA mutation carriers. Firstly, we identified a de novo, missense mutation (c.238C>G, p.(Leu80Val)) in a five-year old Indian boy who presented with periventricular nodular heterotopia, increased skin laxity, joint hypermobility, mitral valve prolapse with regurgitation and marked facial features (e.g. a flat face, orbital fullness, upslanting palpebral fissures and low-set ears). Secondly, we identified two cis-located FLNA mutations (c.7921C>G, p.(Pro2641Ala); c.7923delC, p.(Tyr2642Thrfs*63)) in a Bosnian patient with Ehlers-Danlos syndrome-like features such as skin translucency and joint hypermobility. This patient also presented with brain anomalies, pectus excavatum, mitral valve prolapse, pulmonary hypertension and dilatation of the pulmonary arteries. He died from heart failure in his second year of life. Conclusions: These two new cases expand the list of live-born FLNA mutation-positive males with connective tissue disease from eight to ten, contributing to a better knowledge of the genetic and phenotypic spectrum of FLNA-related disease.

Original languageEnglish
Article number140
JournalBMC Medical Genetics
Volume19
Issue number1
DOIs
Publication statusPublished - 08-08-2018

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Filamins
Connective Tissue
Mutation
Joint Instability
Mitral Valve Prolapse
Periventricular Nodular Heterotopia
Funnel Chest
Ehlers-Danlos Syndrome
Microfilament Proteins
X-Linked Genes
Skin
Connective Tissue Diseases
Eyelids
Missense Mutation
Pulmonary Hypertension
Pulmonary Artery
Ear
Dilatation
Heart Failure
Genotype

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Cannaerts, Elyssa ; Shukla, Anju ; Hasanhodzic, Mensuda ; Alaerts, Maaike ; Schepers, Dorien ; Van Laer, Lut ; Girisha, Katta M. ; Hojsak, Iva ; Loeys, Bart ; Verstraeten, Aline. / FLNA mutations in surviving males presenting with connective tissue findings : Two new case reports and review of the literature. In: BMC Medical Genetics. 2018 ; Vol. 19, No. 1.
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FLNA mutations in surviving males presenting with connective tissue findings : Two new case reports and review of the literature. / Cannaerts, Elyssa; Shukla, Anju; Hasanhodzic, Mensuda; Alaerts, Maaike; Schepers, Dorien; Van Laer, Lut; Girisha, Katta M.; Hojsak, Iva; Loeys, Bart; Verstraeten, Aline.

In: BMC Medical Genetics, Vol. 19, No. 1, 140, 08.08.2018.

Research output: Contribution to journalArticle

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AU - Cannaerts, Elyssa

AU - Shukla, Anju

AU - Hasanhodzic, Mensuda

AU - Alaerts, Maaike

AU - Schepers, Dorien

AU - Van Laer, Lut

AU - Girisha, Katta M.

AU - Hojsak, Iva

AU - Loeys, Bart

AU - Verstraeten, Aline

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Y1 - 2018/8/8

N2 - Background: Mutations in the X-linked gene filamin A (FLNA), encoding the actin-binding protein FLNA, cause a wide spectrum of connective tissue, skeletal, cardiovascular and/or gastrointestinal manifestations. Males are typically more severely affected than females with common pre- or perinatal death. Case presentation: We provide a genotype- and phenotype-oriented literature overview of FLNA hemizygous mutations and report on two live-born male FLNA mutation carriers. Firstly, we identified a de novo, missense mutation (c.238C>G, p.(Leu80Val)) in a five-year old Indian boy who presented with periventricular nodular heterotopia, increased skin laxity, joint hypermobility, mitral valve prolapse with regurgitation and marked facial features (e.g. a flat face, orbital fullness, upslanting palpebral fissures and low-set ears). Secondly, we identified two cis-located FLNA mutations (c.7921C>G, p.(Pro2641Ala); c.7923delC, p.(Tyr2642Thrfs*63)) in a Bosnian patient with Ehlers-Danlos syndrome-like features such as skin translucency and joint hypermobility. This patient also presented with brain anomalies, pectus excavatum, mitral valve prolapse, pulmonary hypertension and dilatation of the pulmonary arteries. He died from heart failure in his second year of life. Conclusions: These two new cases expand the list of live-born FLNA mutation-positive males with connective tissue disease from eight to ten, contributing to a better knowledge of the genetic and phenotypic spectrum of FLNA-related disease.

AB - Background: Mutations in the X-linked gene filamin A (FLNA), encoding the actin-binding protein FLNA, cause a wide spectrum of connective tissue, skeletal, cardiovascular and/or gastrointestinal manifestations. Males are typically more severely affected than females with common pre- or perinatal death. Case presentation: We provide a genotype- and phenotype-oriented literature overview of FLNA hemizygous mutations and report on two live-born male FLNA mutation carriers. Firstly, we identified a de novo, missense mutation (c.238C>G, p.(Leu80Val)) in a five-year old Indian boy who presented with periventricular nodular heterotopia, increased skin laxity, joint hypermobility, mitral valve prolapse with regurgitation and marked facial features (e.g. a flat face, orbital fullness, upslanting palpebral fissures and low-set ears). Secondly, we identified two cis-located FLNA mutations (c.7921C>G, p.(Pro2641Ala); c.7923delC, p.(Tyr2642Thrfs*63)) in a Bosnian patient with Ehlers-Danlos syndrome-like features such as skin translucency and joint hypermobility. This patient also presented with brain anomalies, pectus excavatum, mitral valve prolapse, pulmonary hypertension and dilatation of the pulmonary arteries. He died from heart failure in his second year of life. Conclusions: These two new cases expand the list of live-born FLNA mutation-positive males with connective tissue disease from eight to ten, contributing to a better knowledge of the genetic and phenotypic spectrum of FLNA-related disease.

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