Terminal osseous dysplasia with pigmentary defects; Case and brief review of filamin <scp>A</scp>‐related disorders

Bhabha, Friyana K; Walsh, Maie; Orchard, David; Savarirayan, Ravi

doi:10.1111/ajd.12367

Cited by 4 publications

(5 citation statements)

References 10 publications

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“…Filamin A is an actin‐binding protein and is known to be important in the pericellular organization of collagen and providing tension to the ECM . Alterations in this protein with age in the skin have not to our knowledge been reported previously, though it is known that mutations in filamin A can lead to cutaneous alterations including fibromas and pigmentary changes . Filamin A is also known to influence TGF‐ β signalling through modulation of RhoA and SMAD trafficking, but also influence the negative regulation of both ERK1/2 and MMP signalling via a RAS‐GRF1 .…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometry‐based proteomics reveals the distinct nature of the skin proteomes of photoaged compared to intrinsically aged skin

Newton

Riba-Garcia

Griffiths

et al. 2019

Intern J of Cosmetic Sci

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Objective With increasing age, skin is subject to alterations in its organization, which impact on its function as well as having clinical consequences. Proteomics is a useful tool for non‐targeted, semi‐quantitative simultaneous investigation of high numbers of proteins. In the current study, we utilize proteomics to characterize and contrast age‐associated differences in photoexposed and photoprotected skin, with a focus on the epidermis, dermal–epidermal junction and papillary dermis. Methods Skin biopsies from buttock (photoprotected) and forearm (photoexposed) of healthy volunteers (aged 18–30 or ≥65 years) were transversely sectioned from the stratum corneum to a depth of 250 μm. Following SDS‐PAGE, each sample lane was segmented prior to analysis by liquid chromatography‐mass spectrometry/mass spectrometry. Pathway analysis was carried out using Ingenuity IPA. Results Comparison of skin proteomes at buttock and forearm sites revealed differences in relative protein abundance. Ageing in skin on the photoexposed forearm resulted in 80% of the altered proteins being increased with age, in contrast to the photoprotected buttock where 74% of altered proteins with age were reduced. Functionally, age‐altered proteins in the photoexposed forearm were associated with conferring structure, energy and metabolism. In the photoprotected buttock, proteins associated with gene expression, free‐radical scavenging, protein synthesis and protein degradation were most frequently altered. Conclusion This study highlights the necessity of not considering photoageing as an accelerated intrinsic ageing, but as a distinct physiological process.

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Section: Discussionmentioning

confidence: 99%

Mass spectrometry‐based proteomics reveals the distinct nature of the skin proteomes of photoaged compared to intrinsically aged skin

Newton

Riba-Garcia

Griffiths

et al. 2019

Intern J of Cosmetic Sci

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“…The filamin A protein is located in the cytoplasm and links actin filaments to membrane glycoproteins, playing an essential role in modeling the cytoskeleton (Bhabha et al, ). It is widely expressed throughout the body and mutations in the FLNA gene have been associated with various different OMIM listed conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Lastly, Bhabha et al () stated that digital fibromas were more prominent during infancy and not a feature in adult age. Histology of digital fibromas in cases with TODPD, are distinct from isolated infantile digital fibromatosis, as the former do not show the characteristic cytoplasmic inclusion bodies within the proliferating cells (Drut et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Skeletal findings include bowing and mesomelic shortening of long bones, abnormal bony texture with osteoporosis and cystic lesions with amorphous ossification of metacarpal, metatarsal and phalangeal disorganization leading to camptodactyly (Brunetti‐Pierri et al, ). Twenty‐eight cases from 14 families all molecularly diagnosed with TODPD have been reported up till now (Bacino et al, ; Baroncini et al, ; Bhabha, Walsh, Orchard, & Savarirayan, ; Bloem, Vuzevski, & Huffstadt, ; Breuning et al, ; Brunetti‐Pierri et al, ; Connor, Shchelochkov, & Ciliberto, ; Drut, Pedemonte, & Rositto, ; Horii, Sugiura, & Nakamura, ; Kokitsu‐Nakata, Antunes, & Guion‐Almeida, ; Sun et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Terminal osseous dysplasia with pigmentary defects (TODPD) in a Turkish girl with new skin findings

Azaklı

Akkaya

Aygün

et al. 2018

American J of Med Genetics Pt A

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Terminal osseous dysplasia with pigmentary defects (TODPD; MIM #300244) is an extremely rare, X-linked dominant, in utero male-lethal disease, characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibromatosis of childhood. Delayed/ abnormal ossification of bones of the hands and feet, joint contractures, and dysmorphic facial features may accompany. A single recurrent mutation (c.5217 G>A) of the FLNA gene which causes cryptic splicing was identified as the cause of the disease. We here present the first TODPD case from Turkey with full-blown phenotype who exhibit unique additional findings, hypopigmented patch on the lower extremity following Blaschko's lines and smooth muscle hamartoma of the scalp in review of all the previously reported TODPD cases. K E Y W O R D S digital fibroma, filamin A, hypopigmented patch, smooth muscle hamartoma, TODPD

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“…TODPD is part of the OPD‐spectrum disorders and is a male‐lethal disease with X‐linked dominant inheritance, characterized by skeletal dysplasia with brachydactyly, camptodactyly, limb deformities, scoliosis, pectus excavatum, and shortened and bowed long bones. Dysmorphic features include recurrent digital fibromata during infancy, multiple frenulae and pigmentary changes of the skin, hypertelorism, colobomata, and short stature (Bhabha et al, 2016 ; Sun et al, 2010 ). Only one single recurrent variant (c.5217G>A) in the FLNA ‐gene is known to be responsible for TODPD (Sun et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Terminal osseous dysplasia with pigmentary defects and cardiomyopathy caused by a novel FLNA variant

Rumping

Wessels

Postma

et al. 2021

American J of Med Genetics Pt A

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Terminal osseous dysplasia with pigmentary defects (TODPD), also known as digitocutaneous dysplasia, is one of the X-linked filaminopathies caused by a variety of FLNA-variants. TODPD is characterized by skeletal defects, skin fibromata and dysmorphic facial features. So far, only a single recurrent variant (c.5217G>A;p.Val1724_Thr1739del) in FLNA has found to be responsible for TODPD. We identified a novel c.5217+5G>C variant in FLNA in a female proband with skeletal defects, skin fibromata, interstitial lung disease, epilepsy, and restrictive cardiomyopathy. This variant causes mis-splicing of exon 31 predicting the production of a FLNA-protein with an in-frame-deletion of 16 residues identical to the miss-splicing-effect of the recurrent TODPD c.5217G>A variant. This mis-spliced transcript was explicitly detected in heart tissue, but was absent from blood, skin, and lung. X-inactivation analyses showed extreme skewing with almost complete inactivation of the mutated allele (>90%) in these tissues, except for heart. The mother of the proband, who also has fibromata and skeletal abnormalities, is also carrier of the FLNA-variant and was diagnosed with noncompaction cardiomyopathy after cardiac screening. No other relevant variants in cardiomyopathy-related genes were found. Here we describe a novel variant in FLNA (c.5217+5G>C) as the second pathogenic variant responsible for TODPD. Cardiomyopathy has not been described as a phenotypic feature of TODPD before.

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Terminal osseous dysplasia with pigmentary defects; Case and brief review of filamin A‐related disorders

Cited by 4 publications

References 10 publications

Mass spectrometry‐based proteomics reveals the distinct nature of the skin proteomes of photoaged compared to intrinsically aged skin

Mass spectrometry‐based proteomics reveals the distinct nature of the skin proteomes of photoaged compared to intrinsically aged skin

Terminal osseous dysplasia with pigmentary defects (TODPD) in a Turkish girl with new skin findings

Terminal osseous dysplasia with pigmentary defects and cardiomyopathy caused by a novel FLNA variant

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