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Pediatric Hematology and Oncology Sep 2021
Topics: Delayed Diagnosis; Heterozygote; Humans; Immunologic Deficiency Syndromes; Lymphohistiocytosis, Hemophagocytic; Mutation; Piebaldism; Primary Immunodeficiency Diseases; rab27 GTP-Binding Proteins
PubMed: 33792483
DOI: 10.1080/08880018.2021.1895925 -
Skin Appendage Disorders Feb 2021Piebaldism is a rare autosomal dominant disorder characterized by leucoderma with leucotrichia. We describe a case of white forelock repigmentation in an infant with...
Piebaldism is a rare autosomal dominant disorder characterized by leucoderma with leucotrichia. We describe a case of white forelock repigmentation in an infant with piebaldism, thanks to a photograph sent by the patient's mother to our dermatology clinic, during COVID-19 pandemic.
PubMed: 33791342
DOI: 10.1159/000512033 -
Scandinavian Journal of Immunology Jun 2021Griscelli syndrome (GS) is a rare autosomal recessive disease with characteristic pigment distribution, and there are currently 3 types according to the underlying... (Meta-Analysis)
Meta-Analysis Review
Griscelli syndrome (GS) is a rare autosomal recessive disease with characteristic pigment distribution, and there are currently 3 types according to the underlying genetic defect and clinical features. We present the case of a girl born from consanguineous parents who presented with predominant neurologic symptoms, silvery hair and granulomatous skin lesions. Cerebral magnetic resonance revealed diffuse white matter lesions, and central nervous system (CNS) lymphocytic infiltration was suspected. The patient underwent haematopoietic stem cell transplantation with graft failure and autologous reconstitution. She developed elevated liver enzyme with a cholestatic pattern. Multiple liver biopsies revealed centrilobular cholestasis and unspecific portal inflammation that improved with immunomodulatory treatment. She was revealed to have an impaired cytotoxicity in NK cells and a decreased expression of RAB27A. However, no variants were found in the gene. All types of GS present with pigment dilution and irregular pigment clumps that can be seen through light microscopy in hair and skin biopsy. Dermic granulomas and immunodeficiency with infectious and HLH predisposition have been described in GS type 2 (GS2). Neurologic alterations might be seen in GS type 1 (GS1) and GS type 2 (GS2), due to different mechanisms. GS1 presents with neurologic impairment secondary to myosin Va role in neuronal development and synapsis. Meanwhile, GS2 can present with neurologic impairment secondary to SNC HLH. Clinical features and cytotoxicity might aid in differentiating GS1 and GS2, especially since treatment differs.
Topics: Biomarkers; Biopsy; Disease Management; Disease Susceptibility; Genetic Predisposition to Disease; Hearing Loss, Sensorineural; Humans; Lymphohistiocytosis, Hemophagocytic; Mutation; Phenotype; Piebaldism; Pigmentation Disorders; Primary Immunodeficiency Diseases; Prognosis
PubMed: 33660295
DOI: 10.1111/sji.13034 -
Donor to recipient ratios in the surgical treatment of vitiligo and piebaldism: a systematic review.Journal of the European Academy of... May 2021Stabilized vitiligo resistant to conventional therapy (e.g. segmental vitiligo) and piebaldism lesions can be treated with autologous cellular grafting techniques, such...
Stabilized vitiligo resistant to conventional therapy (e.g. segmental vitiligo) and piebaldism lesions can be treated with autologous cellular grafting techniques, such as non-cultured cell suspension transplantation (NCST) and cultured melanocyte transplantation (CMT). These methods are preferred when treating larger surface areas due to the small amount of donor skin needed. However, the donor to recipient expansion ratios and outcomes reported in studies with cellular grafting vary widely, and to date, no overview or guideline exists on the optimal ratio. The aim of our study was to obtain an overview of the various expansion ratios used in cellular grafting and to identify whether expansion ratios affect repigmentation and colour match. We performed a systematic literature search in MEDLINE and EMBASE to review clinical studies that reported the expansion ratio and repigmentation after cellular grafting. We included 31 eligible clinical studies with 1591 patients in total. Our study provides an overview of various expansion ratios used in cellular grafting for vitiligo and piebaldism, which varied from 1:1 up to 1:100. We found expansion ratios between 1:1 and 1:10 for studies investigating NCST and from 1:20 to 1:100 in studies evaluating CMT. Pooled analyses of studies with the same expansion ratio and repigmentation thresholds showed that when using the lowest (1:3) expansion ratio, the proportion of lesions achieving >50% or >75% repigmentation after NCST was significantly better than when using the highest (1:10) expansion ratio (χ P = 0.000 and χ P = 0.006, respectively). Less than half of our included studies stated the colour match between different expansion ratios, and results were variable. In conclusion, the results of our study indicate that higher expansion ratios lead to lower repigmentation percentages after NCST treatment. This should be taken into consideration while determining which expansion ratio to use for treating a patient.
Topics: Humans; Melanocytes; Piebaldism; Skin Pigmentation; Skin Transplantation; Transplantation, Autologous; Treatment Outcome; Vitiligo
PubMed: 33428279
DOI: 10.1111/jdv.17108 -
Frontiers in Immunology 2020Griscelli syndrome type 2 (GS-2) is an inborn error of immunity characterized by partial albinism and episodes of hemophagocytic lymphohistiocytosis (HLH). It is caused...
Griscelli syndrome type 2 (GS-2) is an inborn error of immunity characterized by partial albinism and episodes of hemophagocytic lymphohistiocytosis (HLH). It is caused by mutations that encode RAB27A, a member of the Rab GTPase family. RAB27A is expressed in many tissues and regulates vesicular transport and organelle dynamics. Occasionally, GS-2 patients with mutation display normal pigmentation. The study of such variants provides the opportunity to map distinct binding sites for tissue-specific effectors on RAB27A. Here we present a new case of GS-2 without albinism (GS-2 sine albinism) caused by a novel missense mutation (Val143Ala) in the RAB27A and characterize its functional cellular consequences. Using pertinent animal cell lines, the Val143Ala mutation impairs both the RAB27A-SLP2-A interaction and RAB27A-MUNC13-4 interaction, but it does not affect the RAB27A-melanophilin (MLPH)/SLAC2-A interaction that is crucial for skin and hair pigmentation. We conclude that disruption of the RAB27A-MUNC13-4 interaction in cytotoxic lymphocytes leads to the HLH predisposition of the GS-2 patient with the Val143Ala mutation. Finally, we include a review of GS-2 sine albinism cases reported in the literature, summarizing their genetic and clinical characteristics.
Topics: Adaptor Proteins, Signal Transducing; Adolescent; Albinism; Animals; Binding Sites; COS Cells; Cell Line; Child; Child, Preschool; Chlorocebus aethiops; Female; Humans; Infant; Infant, Newborn; Leukocytes, Mononuclear; Lymphohistiocytosis, Hemophagocytic; Male; Membrane Proteins; Mutation, Missense; Piebaldism; Primary Immunodeficiency Diseases; rab GTP-Binding Proteins; rab27 GTP-Binding Proteins
PubMed: 33362801
DOI: 10.3389/fimmu.2020.612977 -
American Journal of Translational... 2020Piebaldism is a rare autosomal dominant disorder characterized by congenital patchy depigmentation of the scalp, forehead, trunk, and limbs. The gene is the mainly...
INTRODUCTION
Piebaldism is a rare autosomal dominant disorder characterized by congenital patchy depigmentation of the scalp, forehead, trunk, and limbs. The gene is the mainly causative gene to this disease. But how is involved in piebaldism remains unclear.
METHODS
Whole exome sequencing was used to explore the genetic cause of a familial case of piebaldism. Sanger sequencing was used to validate the variant. To further examine the variant's pathogenicity, the wild type and the mutated plasmids were constructed and transfected into HEK293T cells. Next STAT5 expression, a signaling target of KIT, was detected by western blotting to explore the potential molecular mechanism of the variant in piebaldism. Based on the classification of the given variant, prenatal diagnosis was further performed in this family.
RESULTS
A novel pathogenic variant of c.2326G>A (NM_000222.2) was identified in this family. The phosphorylation of STAT5 was reduced in the mutant transfected cells compared to the wild type after stem cell factor (SCF) treatment, indicating that the KIT signaling was dysfunctional and supported that the variant was a pathogenic one. Prenatal diagnosis results indicated that the fetus exhibited the same genotype as the proband.
CONCLUSION
We identified a novel pathogenic variant in the patient with piebaldism to expand the variation spectrum of . The functional study indicated that the mutant KIT was dysfunctional in KIT signaling. The pathogenic variant identification enriches the knowledge about the genotype/phenotype correlation and could serve as the basis for genetic counseling and prenatal diagnosis.
PubMed: 33194047
DOI: No ID Found -
The Journal of Dermatology Feb 2021
Topics: Humans; Japan; Mutation; Pedigree; Piebaldism; Proto-Oncogene Proteins c-kit
PubMed: 33155701
DOI: 10.1111/1346-8138.15684 -
American Journal of Medical Genetics.... Dec 2020
Topics: Adolescent; Humans; Male; Mutation; Phenotype; Piebaldism; Snail Family Transcription Factors; Waardenburg Syndrome
PubMed: 32975012
DOI: 10.1002/ajmg.a.61887 -
Pediatric Dermatology Jan 2021Griscelli syndrome type 2 is a rare autosomal recessive disorder characterized by hypopigmentation, silvery hair, and immunological dysfunction with no primary...
Griscelli syndrome type 2 is a rare autosomal recessive disorder characterized by hypopigmentation, silvery hair, and immunological dysfunction with no primary neurological impairment. We report an 18-month-old girl with Griscelli syndrome type 2 who presented to the dermatology department for cutaneous granulomas that developed following live-attenuated vaccination. Two compound heterozygous variants in the RAB27A gene were subsequently identified. She developed hemophagocytic lymphohistiocytosis, the key immunological concern, at age 5 years.
Topics: Child, Preschool; Female; Granuloma; Humans; Immunologic Deficiency Syndromes; Infant; Lymphohistiocytosis, Hemophagocytic; Piebaldism; Primary Immunodeficiency Diseases
PubMed: 32965739
DOI: 10.1111/pde.14370 -
PloS One 2020The births of domestic dogs with pigment deletion and associated congenital hearing and/or vision impairments are increasing, as a result of mutations of certain genes...
Are dogs with congenital hearing and/or vision impairments so different from sensory normal dogs? A survey of demographics, morphology, health, behaviour, communication, and activities.
The births of domestic dogs with pigment deletion and associated congenital hearing and/or vision impairments are increasing, as a result of mutations of certain genes expressing popular coat colour patterns (Merle, piebald, Irish spotting). The future of these dogs is often pessimistic (early euthanasia or placement in rescues/fosters, lack of interactions and activities for adults). These pessimistic scenarios result from popular assumptions predicting that dogs with congenital hearing/vision impairments exhibit severe Merle-related health troubles (cardiac, skeletal, neurological), impairment-related behavioural troubles (aggressiveness, anxiety), and poor capacities to communicate, to be trained, and to be engaged in leisure or work activities. However, there is no direct scientific testing, and hence no evidence or refutation, of these assumptions. We therefore addressed an online questionnaire to owners of 223 congenitally sensory impaired (23 vision impaired, 63 hearing impaired, 137 hearing and vision impaired) and 217 sensory normal dogs from various countries. The sensory normal cohort was matched in age, lifetime with owner, breed and sex with the sensory impaired cohort, and was used as a baseline. The questionnaire assessed demographics, morphology, sensory impairments, health and behavioural troubles, activities, and dog-owner communication. Most hearing and/or vision impaired dogs exhibited abnormal pigment deletion in their coat and irises. Vision impaired dogs additionally exhibited ophthalmic abnormalities typically related to Merle. The results are opposed to all above-listed assumptions, except for neurological troubles, which were more frequently reported in sensory impaired dogs. However, we suggest that this finding could be partially accounted for by a lack of diagnosis of breed-related drug sensitivity and impairment-related compulsive behaviours. Results about communication and activities are particularly optimistic. The need for future studies of numerous dogs from various breeds tested for Merle, piebald and medical-drug-resistance genes, and the beneficial effects that present and future research may have on the future of sensory impaired dogs, are discussed.
Topics: Animals; Behavior, Animal; Blindness; Breeding; Communication; Dog Diseases; Dogs; Female; Hearing Loss; Humans; Male; Pets; Pigmentation; Surveys and Questionnaires
PubMed: 32886662
DOI: 10.1371/journal.pone.0230651