OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree. RESULTS: The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual. CONCLUSION The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.
Adenosine Deaminase/genetics* ; China ; Female ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To analyze the clinical features and genetic basis for a Chinese pedigree affected with hereditary dyschromatosis symmetrica hereditaria (DSH). METHODS: Peripheral blood samples of the proband and his mother were collected and subjected to PCR and Sanger sequencing. RESULTS: The patient has conformed to the typical pattern of DSH and manifested with hyperpigmentation, hypo- and hyperpigmentation spots on the back of hands, feet and face. Sanger sequencing confirmed that the proband and his mother have both harbored heterozygous splicing variant c.2762+1G>T in exon 9 of the ADAR gene, which was unreported previously. The same variant was not detected among 100 healthy controls. According to the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PM2+PP4). CONCLUSION The c.2762+1G>T variant of the ADAR gene probably underlay the DSH in this pedigree. Above finding has enriched the spectrum of ADAR gene mutations.
Adenosine Deaminase/genetics* ; China ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To detect variants of ADAR1 gene in two Chinese pedigrees affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: Clinical data and peripheral blood samples of the pedigrees were collected. All exons of the ADAR1 gene were amplified by PCR and subjected to Sanger sequencing. Suspected pathogenic variants were validated among other members of the pedigrees and 100 unrelated healthy controls. RESULTS: For pedigree 1, Sanger sequencing has identified a heterozygous missense variant c.3002G>C (p.Asp968His) in exon 11 of the ADAR1 gene in the proband and his father. For pedigree 2, a novel nonsense variant c.3145C>T (p.Gln1049Ter) was identified in exon 12 of the ADAR1 gene in the proband and his son, which were previously unreported and absent among the healthy controls. CONCLUSION The c.3002G>C (p.Asp968His) and c.3145C>T (p.Gln1049Ter)variants of the ADAR1 gene probably underlay the DSH in the two pedigrees.
Adenosine Deaminase/genetics* ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/genetics* ; RNA-Binding Proteins/genetics*

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a progressive degenerative white matter disorder caused by mutations in the tyrosine kinase domain of the CSF1R gene. ALSP is often misdiagnosed as other diseases due to its rarity and various clinical presentations such as Parkinsonism, pyramidal signs, cognitive impairment and/or psychiatric symptoms. We describe an autopsy case of ALSP with a CSF1R mutation. A 61-year-old woman presented insidious-onset gait difficulty for 12 years since her age of 49, and premature ovarian failure since her age of 35. At initial hospital visit, brain magnetic resonance imaging revealed hydrocephalus. Initially, Parkinson's syndrome was diagnosed, and she was prescribed L-dopa/carbidopa because of spasticity and rigidity of extremities, which had worsened. Subsequently, severe neuropsychiatric symptoms and cognitive impairment developed and radiologically, features of leukoencephalopathy or leukodystrophy were detected. She showed a down-hill course and died, 12 years after initial diagnosis. At autopsy, the brain showed severe symmetric atrophy of bilateral white matter, paper-thin corpus callosum, thin internal capsule, and marked hydrocephalus. Microscopically, diffuse loss of white matter, relatively preserved subcortical U-fibers, and many eosinophilic bulbous neuroaxonal spheroids were noted, but there was no calcification. Pigmented glia with brown cytoplasmic pigmentation were readily found in the white matter, which were positive for Periodic acid-Schiff, p62, and CD163 stains, but almost negative for CD68. Whole-exome and Sanger sequencing revealed a CSF1R mutation (c.2539G>A, p.Glu847Lys) which was reported in prior one ALSP case. This example demonstrates that ALSP could be associated with premature ovarian failure.
Atrophy ; Autopsy ; Axons ; Brain ; Cognition Disorders ; Coloring Agents ; Corpus Callosum ; Cytoplasm ; Diagnosis ; Eosinophils ; Extremities ; Female ; Gait ; Humans ; Hydrocephalus ; Internal Capsule ; Leukoencephalopathies ; Magnetic Resonance Imaging ; Middle Aged ; Muscle Spasticity ; Neuroglia ; Parkinsonian Disorders ; Pigmentation ; Primary Ovarian Insufficiency ; Protein-Tyrosine Kinases ; White Matter

OBJECTIVE: To detect mutations of ADAR gene in two pedigrees affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: Potential mutations of the ADAR gene were analyzed by Sanger sequencing of the probands from both pedigrees. Suspected mutations were validated by Sanger sequencing of other patients from both pedigrees as well as unrelated healthy individuals. RESULTS: A heterozygous nonsense mutation c.1325C>G (p.Ser442Ter) and a novel nonsense mutation c.1498C>T (p.Gln500Ter) were respectively identified in the ADAR gene among all patients from the two pedigrees but not among 200 healthy individuals. CONCLUSION Mutations of the ADAR gene probably underlie the DSH in the two pedigrees. Above findings have enriched the spectrum of ADAR gene mutation.
Adenosine Deaminase ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders ; congenital ; genetics ; RNA-Binding Proteins

Hypomelanosis of Ito (HI) is a neurocutaneous disorder, also known as incontinentia pigmenti achromians. HI has been associated with chromosomal abnormalities, especially mosaicism. Herein, we report a case of HI with multiple congenital anomalies. A 2-month-old girl presented with multiple linear and whorling hypopigmentation on the face, trunk, and both extremities and patch alopecia on the scalp. Moreover, she had conical teeth, aniridia of the both eyes, and multiple musculoskeletal problems, including syndactyly and coccyx deviation. Cytogenetic analysis on peripheral blood was normal 46, XX, and no mutation was found in IKBKG gene test.
Alopecia ; Aniridia ; Chromosome Aberrations ; Coccyx ; Cytogenetic Analysis ; Extremities ; Female ; Humans ; Hypopigmentation ; Infant ; Karyotype ; Mosaicism ; Neurocutaneous Syndromes ; Pigmentation Disorders ; Scalp ; Syndactyly ; Tooth

No abstract available.
Skin Abnormalities ; Herpesviridae Infections ; Pigmentation Disorders ; Hamartoma

PURPOSE: To report a delayed onset of multiple evanescent white dot syndrome in a patient with punctate inner choroidopathy. CASE SUMMARY: A 23-year-old female complained about sudden visual loss in the right eye. Best-corrected visual acuity (BCVA) was 20/100 in the right eye and 20/20 in the left eye. In fundus examination and optical coherence tomographic images, subfoveal choroidal neovascularization (CNV) with hemorrhage was observed in the right eye, accompanied by multiple lesions of atrophic pigmentation on the posterior pole in both eyes. We diagnosed the patient as punctate inner choroidopathy (PIC) and CNV in the right eye, and treated her using three monthly intravitreal injections of bevacizumab (Avastin®, Roche, Basel, Switzerland; 1.25 mg/0.05 mL). The CNV regressed and the BCVA improved to 20/20. Two years later, she complained of visual impairment in her left eye. The BCVA was 20/40. Fundus photography revealed numerous small white dots around the posterior pole and optic disc. Disruption of the photoreceptor layer was seen in optical coherence tomography images. Small white dots were observed as multiple hyperfluorescent dots in fluorescein angiography and hypofluorescent spots in indocyanine green angiography. An enlarged blind spot was observed in the visual field. We diagnosed her as multiple evanescent white dot syndrome (MEWDS). One month after systemic steroid treatment, the multiple white dots disappeared and the BCVA improved to 20/20. CONCLUSIONS: We determined that PIC and MEWDS, which belong to the white dot syndrome, could occur in a patient at different times.
Angiography ; Bevacizumab ; Choroidal Neovascularization ; Female ; Fluorescein Angiography ; Hemorrhage ; Humans ; Indocyanine Green ; Intravitreal Injections ; Optic Disk ; Photography ; Pigmentation ; Switzerland ; Tomography, Optical Coherence ; Vision Disorders ; Visual Acuity ; Visual Fields ; Young Adult

Acquired brachial cutaneous dyschromatosis (ABCD) is an acquired disorder of pigmentary change that presents as chronic, asymptomatic, geographic-shaped, gray-brown patches, consisting of mixed hyper and hypopigmented macules on the dorsal aspect of the forearms. We report a case of a 40-year-old male who presented with asymptomatic, multiple brown-colored macules on the outer aspects of both arms. He had no history of hypertension and had never taken angiotensin converting enzyme inhibitors. He also denied chronic sun exposure history. Histologic examination demonstrated epidermal atrophy, increased basal layer pigmentation, and several telangiectatic vessels in the upper dermis. Solar elastosis was not remarkable. The patient's clinical and histopathologic features were consistent with a diagnosis of ABCD. Poikiloderma of Civatte, melasma, acquired bilateral telangiectatic macules and other pigmentary disorders should be considered in the differential diagnosis of ABCD. Herein, we report a case of ABCD in a middle-aged male without hypertension and medication.
Adult ; Angiotensin-Converting Enzyme Inhibitors ; Arm ; Atrophy ; Dermis ; Diagnosis ; Diagnosis, Differential ; Forearm ; Humans ; Hypertension ; Male* ; Melanosis ; Middle Aged* ; Pigmentation ; Pigmentation Disorders ; Solar System

BACKGROUND: Argyria is a rare irreversible cutaneous pigmentation disorder caused by prolonged exposure to silver. Herein, we report a case of generalized argyria that developed after chronic ingestion of soluble silver-nano particles and presented with muscle weakness. CASE PRESENTATION: A 74-year-old woman visited our emergency room, complaining of fever and mental deterioration. She was diagnosed with acute pyelonephritis and recovered after antibiotic therapy. At presentation, diffuse slate gray-bluish pigmented patches were noticed on her face and nails. Two months prior to visiting our hospital, she was diagnosed with inflammatory myopathy and given steroid therapy at another hospital. We performed a nerve conduction study that revealed polyneuropathy. In skin biopsies from pigmented areas of the forehead and nose, the histopathologic results showed brown-black granules in basement membranes of sweat gland epithelia, which are diagnostic findings of argyria. We reviewed pathology slides obtained from the left thigh muscles and found markedly degenerated myofibers with disorganization of myofibrils without inflammatory reactions, consistent with unspecified myopathy, rather than inflammatory myopathy. The patient was diagnosed with generalized argyria with polyneuropathy and myopathy and transferred to a rehabilitation institution after being tapered off of steroids. CONCLUSIONS: Clinicians should be aware of clinical manifestations of argyria and consider it in differential diagnosis when they examine patients who present with skin pigmentation and muscle weakness.
Aged ; Argyria* ; Basement Membrane ; Biopsy ; Diagnosis, Differential ; Eating ; Emergency Service, Hospital ; Female ; Fever ; Forehead ; Humans ; Muscle Weakness* ; Muscles ; Muscular Diseases ; Myofibrils ; Myositis ; Neural Conduction ; Nose ; Pathology ; Pigmentation Disorders ; Polyneuropathies ; Pyelonephritis ; Rehabilitation ; Silver ; Skin ; Skin Pigmentation ; Steroids ; Sweat Glands ; Thigh