A novel truncating mutation in FLNA causes periventricular nodular heterotopia, Ehlers-Danlos-like collagenopathy and macrothrombocytopenia

Ieda, Daisuke; Hori, Ikumi; Nakamura, Yuji; Ohshita, Hironori; Negishi, Yutaka; Shinohara, Tsutomu; Hattori, Ayako; Kato, Tatsuya; Inukai, Sachiko; Kitamura, Katsumasa; Ohara, Osamu; Kunishima, Shinji; Saitoh, Shinji

doi:10.1016/j.braindev.2018.01.010

Cited by 17 publications

(16 citation statements)

References 8 publications

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“…In the literature review, we found a male/female ratio of 39/148 (79% females) (Table S2). This is in line with the X-linked inheritance of FLNA-PVNH where the vast majority of reported patients are female 12 17. In most hemizygous males the condition is lethal either prenatally or during the neonatal period 12 14 33.…”

Section: Discussion Sudden Inability To Hold On To Thingssupporting

confidence: 75%

“…Extracerebral manifestations include various cardiovascular anomalies (patent ductus arteriosus, atrial or ventricular septal defect, cardiac valve disease, dilatation of the sinuses of Valsalva or the thoracic aorta, stroke and aneurysm formation), thrombocytopenia, gastric immotility and pulmonary disease 5 13 16. Moreover, connective tissue and vascular anomalies of classic Ehlers-Danlos syndrome (EDS) have been reported in some FLNA-PVNH patients 12 13 17–19. The great variability in the phenotypic spectrum observed in PVNH patients with an FLNA variant is not fully clarified nor described 14…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic manifestations inFLNA-related periventricular nodular heterotopia: a case report and review of the literature

et al. 2022

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Periventricular nodular heterotopia (PVNH) is an X-linked disease caused by loss-of-function variants in the filamin A (FLNA) gene. FLNA-PVNH is a heterogeneous disorder, and the phenotype is associated with neurological and non-neurological features including cardiovascular, gastrointestinal, pulmonary, haematological, cutaneous and skeletal manifestations. No clear definition of the FLNA-PVNH phenotype has been established, but the patients are predominantly females with seizures, cardiovascular manifestations, and normal intelligence or mild intellectual disability. Herein, we describe a PVNH patient diagnosed with a novel heterozygous missense variant in FLNA after an atypical presentation of deep vein thrombosis and thrombocytopenia. Clinical evaluation found hypermobility, cardiovascular and skin manifestations. Moreover, we conducted a literature review of 186 FLNA-PVNH patients to describe the phenotypic spectrum. In conclusion, our patient highlights the importance of thorough clinical evaluation to identify manifestations in this very heterogeneous disorder. The phenotypic review may guide clinicians in the assessment and follow-up of FLNA-PVNH patients.

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Section: Discussion Sudden Inability To Hold On To Thingssupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Phenotypic manifestations inFLNA-related periventricular nodular heterotopia: a case report and review of the literature

et al. 2022

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“…[11][12][13][14][15] Mutations in FLNA can cause several diseases, including otopalatodigital syndromes types I and II, frontometaphyseal dysplasia, Melnick-Needles syndrome, periventricular nodular heterotopia, cardiac valvular dysplasia and Ehlers-Danlos syndrome-like collagenopathy. 12,15 It is noteworthy that patients with X-linked inheritance with skin-skeleton-digital fibroma manifestation need to be screened for FLNA mutation. Furthermore, a thorough examination of different organ systems is necessary in TODPD patients with the FLNA mutation, which can mediate organogenesis in multiple systems.…”

Section: Discussionmentioning

confidence: 99%

“…The FLNA gene maps to Xq28 and encodes the actin‐binding cytoplasmic cross‐linking phosphoprotein filamin A (FLNA), also named filamin‐1 or ABP‐280, which is capable of regulating actin cytoskeletal reorganization by interacting with integrins, transmembrane receptor complexes and secondary messengers, and is mainly involved in cytoskeleton remodeling, neurogenesis, cardiovascular malformations and connective tissue abnormalities . Mutations in FLNA can cause several diseases, including otopalatodigital syndromes types I and II, frontometaphyseal dysplasia, Melnick–Needles syndrome, periventricular nodular heterotopia, cardiac valvular dysplasia and Ehlers–Danlos syndrome‐like collagenopathy . It is noteworthy that patients with X‐linked inheritance with skin–skeleton–digital fibroma manifestation need to be screened for FLNA mutation.…”

Section: Discussionmentioning

confidence: 99%

Terminal osseous dysplasia with pigmentary defects in a Chinese girl with the FLNA mutation: A case report and published work review

Xie

Xiao

et al. 2020

The Journal of Dermatology

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Terminal osseous dysplasia with pigmentary defects (TODPD) is an extremely rare X‐linked dominant syndrome characterized by pigmentary skin defects, cutaneous digital fibromas and skeletal anomalies. Recent studies have identified that TODPD is caused by a unique variant, c.5217G>A (p.Val1724_Thr1739del), in the FLNA gene, which could in turn lead to the elastic fiber abnormality in TODPD. We herein present a rare case of TODPD in a Chinese girl due to an FLNA c.5217G>A heterozygous mutation, but the skin lesion biopsy showed that the elastic fibers were within normal limits in the dermis. A published work review of TODPD with the FLNA mutation from various origins is also included in this paper. To the best of our knowledge, this is the first report on TODPD with the FLNA mutation in China.

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“…In humans, FLNA mutations lead to a broad spectrum of clinical disorders, called filaminopathies, which can be classified in loss of function or gain of function. FLNA loss-of-function mutations, leading to reduced or absent FLNA expression, are embryonic lethal in males but are manifest in females as periventricular nodular heterotopia (PVNH), a localized neuronal migration disorder during late embryonic and early fetal development, Ehlers-Danlos syndrome-like collagenopathy, macrothrombocytopenia and X-linked cardiac valvular dystrophy (XCVD) (Fox et al 1998, Sheen et al 2005, Bernstein et al 2011, Ieda et al 2018. FLNA variants can also present with seizures, cardiovascular and pulmonary findings (Robertson 2005).…”

Section: Flna: Structure and Functionmentioning

confidence: 99%

Cytoskeleton actin-binding proteins in clinical behavior of pituitary tumors

Mantovani

Treppiedi

Giardino

et al. 2019

Endocrine-Related Cancer

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Although generally benign, pituitary tumors are frequently locally invasive, with reduced success of neurosurgery and unresponsive to pharmacological treatment with somatostatin or dopamine analogues. The molecular basis of the different biological behavior of pituitary tumors are still poorly identified, but a body of work now suggests that the activity of specific cytoskeleton proteins is a key factor regulating both the invasiveness and drug resistance of these tumors. This review recapitulates the experimental evidence supporting a role for the actin-binding protein filamin A (FLNA) in the regulation of somatostatin and dopamine receptors expression and signaling in pituitary tumors, thus in determining the responsiveness to currently used drugs, somatostatin analogues and dopamine receptor type 2 agonists. Regarding the regulation of invasive behavior of pituitary tumoral cells, we bring evidence to the role of the actin-severing protein cofilin, whose activation status may be modulated by dopaminergic and somatostatinergic drugs, through FLNA involvement. Molecular mechanisms involved in the regulation of FLNA expression and function in pituitary tumors will also be discussed.

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A novel truncating mutation in FLNA causes periventricular nodular heterotopia, Ehlers-Danlos-like collagenopathy and macrothrombocytopenia

Cited by 17 publications

References 8 publications

Phenotypic manifestations inFLNA-related periventricular nodular heterotopia: a case report and review of the literature

Phenotypic manifestations inFLNA-related periventricular nodular heterotopia: a case report and review of the literature

Terminal osseous dysplasia with pigmentary defects in a Chinese girl with the FLNA mutation: A case report and published work review

Cytoskeleton actin-binding proteins in clinical behavior of pituitary tumors

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