Publications by authors named "Satyamaanasa Polubothu"

12 Publications

  • Page 1 of 1

Keratinocytic epidermal nevi associated with localized fibro-osseous lesions without hypophosphatemia.

Pediatr Dermatol 2020 Sep 14;37(5):890-895. Epub 2020 Jul 14.

Department of Dermatology, University Hospitals of Leuven, Leuven, Belgium.

Keratinocytic epidermal nevi (KEN) are characterized clinically by permanent hyperkeratosis in the distribution of Blaschko's lines and histologically by hyperplasia of epidermal keratinocytes. KEN with underlying RAS mutations have been associated with hypophosphatemic rickets and dysplastic bone lesions described as congenital cutaneous skeletal hypophosphatemia syndrome. Here, we describe two patients with keratinocytic epidermal nevi, in one associated with a papular nevus spilus, who presented with distinct localized congenital fibro-osseous lesions in the lower leg, diagnosed on both radiology and histology as osteofibrous dysplasia, in the absence of hypophosphatemia or rickets, or significantly raised FGF23 levels but with distinct mosaic HRAS mutations. This expands the spectrum of cutaneous/skeletal mosaic RASopathies and alerts clinicians to the importance of evaluating for bony disease even in the absence of bone profile abnormalities.
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http://dx.doi.org/10.1111/pde.14254DOI Listing
September 2020

brain somatic pathogenic variant in an individual with phacomatosis pigmentovascularis.

Neurol Genet 2019 Dec 30;5(6):e366. Epub 2019 Oct 30.

Baylor College of Medicine (J.M.S., S.C.M.), Houston, TX; Texas Children's Hospital (L.Z.R., H.S., G.L., V.R., J.V.H., D.J.C., F.S., A.M.A., I.A., L.C.B., D.M.); Department of Molecular and Human Genetics (L.Z.R., H.S., H.D., F.S., L.C.B., D.M.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (P.B.), Northwell Health, Division of Human Genetics and Genomics, Great Neck, NY; Department of Pathology and Immunology (Y.-S.L.), Washington University School of Medicine, St. Louis, MO; Genetics and Genomic Medicine (S.P., V.K.), UCL GOS Institute of Child Health; Pediatric Dermatology (S.P., V.K.), Great Ormond Street Hospital for Children, London, UK; Department of Dermatology (G.L., V.R.), Department of Radiology (J.V.H.), and Department of Neurosurgery (D.J.C.), Baylor College of Medicine, Houston, TX; Joint BCM-CUHK Center of Medical Genetics (F.S.), Prince of Wales Hospital, ShaTin, Hong Kong SAR; Department of Pathology and Immunology (A.M.A), Department of Pediatrics (I.A.), and Department of Neurology (I.A.), Baylor College of Medicine, Houston, TX; and Department of Pediatrics (D.M.), Faculty of Medicine, Kuwait University, Safat, Kuwait.

Objective: To describe the findings of histopathology and genotyping studies in affected brain tissue from an individual with phacomatosis pigmentovascularis (PPV).

Methods: A retrospective chart review of a 2-year 10-month-old male with a clinical diagnosis of PPV cesiomarmorata (or type V) was performed. Clinical features, brain imaging and histopathology findings, and genotyping studies in his affected brain tissue are summarized.

Results: The proband had a clinically severe neurologic phenotype characterized by global developmental delay, generalized hypotonia, and recurrent episodes of cardiac asystole in the setting of status epilepticus. A somatic pathogenic variant in (c.547C>T, p.Arg183Cys) was detected in his skin tissue but not in blood (previously published). He underwent an urgent left posterior quadrantectomy for his life-threatening seizures. Histopathology of resected brain tissue showed an increase in leptomeningeal melanocytes and abnormal vasculature, and the exact pathogenic variant in (c.547C>T, p.Arg183Cys), previously isolated from his skin tissue but not blood, was detected in his resected brain tissue.

Conclusions: The finding of this variant in affected skin and brain tissue of our patient with PPV supports a unifying genetic diagnosis of his neurocutaneous features.
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http://dx.doi.org/10.1212/NXG.0000000000000366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878837PMC
December 2019

GNA11 Mutation as a Cause of Sturge-Weber Syndrome: Expansion of the Phenotypic Spectrum of G Mosaicism and the Associated Clinical Diagnoses.

J Invest Dermatol 2020 05 12;140(5):1110-1113. Epub 2019 Dec 12.

Great Ormond St Hospital for Children NHS Foundation Trust, and UCL GOS Institute of Child Health, London, United Kingdom; Mosaicism and Precision Medicine Laboratory, The Francis Crick Institute, London, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2019.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187890PMC
May 2020

Postzygotic inactivating mutations of RHOA cause a mosaic neuroectodermal syndrome.

Nat Genet 2019 10 30;51(10):1438-1441. Epub 2019 Sep 30.

Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement, Centre Hospitalier Universitaire Dijon Bourgogne, Dijon, France.

Hypopigmentation along Blaschko's lines is a hallmark of a poorly defined group of mosaic syndromes whose genetic causes are unknown. Here we show that postzygotic inactivating mutations of RHOA cause a neuroectodermal syndrome combining linear hypopigmentation, alopecia, apparently asymptomatic leukoencephalopathy, and facial, ocular, dental and acral anomalies. Our findings pave the way toward elucidating the etiology of pigmentary mosaicism and highlight the role of RHOA in human development and disease.
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http://dx.doi.org/10.1038/s41588-019-0498-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858542PMC
October 2019

Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy.

J Clin Invest 2018 04 12;128(4):1496-1508. Epub 2018 Mar 12.

Genetics and Genomic Medicine, University College London (UCL) Great Ormond Street Institute of Child Health, London, United Kingdom.

Background: Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options are severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous malformations (AVM).

Methods: To investigate the pathogenesis of sporadic intracranial and extracranial VMs in 160 children in which known genetic causes had been excluded, we sequenced DNA from affected tissue and optimized analysis for detection of low mutant allele frequency.

Results: We discovered multiple mosaic-activating variants in 4 genes of the RAS/MAPK pathway, KRAS, NRAS, BRAF, and MAP2K1, a pathway commonly activated in cancer and responsible for the germline RAS-opathies. These variants were more frequent in high-flow than low-flow VMs. In vitro characterization and 2 transgenic zebrafish AVM models that recapitulated the human phenotype validated the pathogenesis of the mutant alleles. Importantly, treatment of AVM-BRAF mutant zebrafish with the BRAF inhibitor vemurafinib restored blood flow in AVM.

Conclusion: Our findings uncover a major cause of sporadic VMs of different clinical types and thereby offer the potential of personalized medical treatment by repurposing existing licensed cancer therapies.

Funding: This work was funded or supported by grants from the AVM Butterfly Charity, the Wellcome Trust (UK), the Medical Research Council (UK), the UK National Institute for Health Research, the L'Oreal-Melanoma Research Alliance, the European Research Council, and the National Human Genome Research Institute (US).
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http://dx.doi.org/10.1172/JCI98589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873857PMC
April 2018

White Eyelashes and Red Eyes in a 7-Year-Old Boy.

Pediatr Dermatol 2017 Sep;34(5):612-613

Genetics and Genomic Medicine, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.

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http://dx.doi.org/10.1111/pde.13213DOI Listing
September 2017

Congenital diaphragmatic hernia-influence of fetoscopic tracheal occlusion on outcomes and predictors of survival.

Eur J Pediatr 2016 Aug 8;175(8):1071-6. Epub 2016 Jun 8.

Neonatal Intensive Care Unit, King's College Hospital, 4th Floor Golden Jubilee Wing, Denmark Hill, London, SE5 9RS, UK.

Unlabelled: The morbidity of infants with congenital diaphragmatic hernia (CDH) who had undergone foetal endoscopic tracheal occlusion (FETO) to those who had not was compared and predictors of survival regardless of antenatal intervention were identified. FETO was undertaken on the basis of the lung to head ratio or the position of the liver. A retrospective review of the records of 78 CDH infants was undertaken to determine the lung-head ratio (LHR) at referral and prior to birth, maximum oxygen saturation in the labour suite and neonatal outcomes. The 43 FETO infants were born earlier (mean 34 versus 38 weeks) (p < 0.001). They had a lower mean LHR at referral (0.65 versus 1.24) (p < 0.001) but not prior to birth and did not have a higher mortality than the 35 non-FETO infants. The FETO infants required significantly longer durations of ventilation (median: 15 versus 6 days) and supplementary oxygen (28 versus 8 days) and hospital stay (29 versus 16 days). Overall, the best predictor of survival was the OI in the first 24 h.

Conclusion: The FETO group had increased morbidity, but not mortality. The lowest oxygenation index in the first 24 h was the best predictor of survival regardless of antenatal intervention.

What Is Known: • Randomised controlled trials have demonstrated that foetal endotracheal occlusion (FETO) in high risk infants with congenital diaphragmatic hernia is associated with a higher survival rate. • Mortality is greater in foetuses who underwent FETO and delivered prior to 35 weeks of gestation. What is New: • Infants who had undergone FETO compared to those who had not had significantly longer durations of mechanical ventilation, supplementary oxygen and hospital stay. • Regardless of antenatal intervention, the lowest oxygenation index in the first 24 h was the best predictor of survival.
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http://dx.doi.org/10.1007/s00431-016-2742-6DOI Listing
August 2016

Autosomal dominant polycystic kidney disease in children.

BMJ 2016 Jun 6;353:i2957. Epub 2016 Jun 6.

Department of Paediatric Nephrology, Evelina London Children's Hospital, London, UK.

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http://dx.doi.org/10.1136/bmj.i2957DOI Listing
June 2016

An audit of prophylactic antibiotic use in laryngeal reconstruction surgery.

Int J Pediatr Otorhinolaryngol 2009 Aug 5;73(8):1157-9. Epub 2009 Jun 5.

Department of Otolaryngology, Royal Hospital for Sick Children, Yorkhill, Glasgow, United Kingdom.

Objective: Published data on the role of antibiotics after open airway reconstruction surgery in children is lacking. We reviewed adherence to our own departmental antibiotic protocol to determine its adequacy and effectiveness.

Methods: We reviewed the records of all children undergoing open airway reconstruction surgery 2003-2007 in our unit which is based in a tertiary referral children's hospital.

Results: 36 children underwent surgery, of whom 32 were given appropriate antibiotic prophylaxis. Failure to give antibiotic prophylaxis was associated with increased rates of infection (wound infection and pneumonia) and with a longer stay in the ITU.

Conclusions: We present a revised antibiotic protocol based on our experience and local antibiotic advice.
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http://dx.doi.org/10.1016/j.ijporl.2009.04.026DOI Listing
August 2009