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The Journal of Investigative Dermatology Nov 2023The melanocyte-keratinocyte transplantation procedure (MKTP) treats stable and recalcitrant vitiligo. Despite careful selection of candidates based on clinical...
The melanocyte-keratinocyte transplantation procedure (MKTP) treats stable and recalcitrant vitiligo. Despite careful selection of candidates based on clinical stability, the success of the procedure is unpredictable. The aim of our study was to define the immunological profile of stable vitiligo lesions undergoing MKTP and correlate them with clinical outcomes. We included 20 MKTP candidates with vitiligo and a patient with piebaldism as a control. Prior to MKTP, T-cell subsets and chemokines in the recipient skin were measured by flow cytometry and ELISA. During MKTP, melanocytes in the donor skin were quantified by flow cytometry. After MKTP, patients were followed for 12 months and repigmentation was assessed clinically and by ImageJ analysis of clinical photographs. Baseline immunologic biomarkers, duration of clinical stability, and transplanted melanocyte number were correlated to postsurgical repigmentation scores. CD8+ T cells were elevated in 43% of the clinically stable vitiligo lesions. CD8+ T-cell number negatively correlated with postsurgical repigmentation scores (r = -0.635, P = 0.002). Duration of clinical stability, skin chemokines, and transplanted melanocyte number did not influence postsurgical repigmentation. This study demonstrates that CD8+ T-cell number correlates negatively with success of postsurgical repigmentation and can be a biomarker to identify ideal surgical candidates.
Topics: Humans; Vitiligo; Melanocytes; CD8-Positive T-Lymphocytes; Male; Female; Adult; Keratinocytes; Middle Aged; Young Adult; Treatment Outcome; Adolescent; Skin Transplantation; Follow-Up Studies
PubMed: 37478900
DOI: 10.1016/j.jid.2023.03.1689 -
Skin Research and Technology : Official... Jun 2023Piebaldism is a rare, autosomal dominant, and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or...
BACKGROUND
Piebaldism is a rare, autosomal dominant, and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SLUG genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder.
METHODS
In this paper, we report a case of piebaldism with café-au-lait macules resulting from a novel mutation of KIT gene c.1982C > T (p.Thr661Ile) in a three-generation Chinese family. The whole-exome sequencing, mitochondrial gene 3000X, and bioinformatics tools were used to identify the mutation in this new-found pedigree. In addition, we searched the databases of "Punmed, Chinese National Knowledge Infrastructure, CMJD, WANFANG MED ONLINE", reviewed 88 cases of piebaldism caused by KIT gene mutation, and summarized the relationship between clinical phenotype and genotype of piebaldism through logistic regression and other statistical methods.
RESULTS
The proband and her affected mother carried a heterozygous c.1982C > T missense mutation (p.Thr661Ile) on KIT gene. Bioinformatics analysis hinted that it had potential pathogenicity. The data showed that piebaldism patients with cafè-au-lait macules had KIT mutations almost located in the intracellular tyrosine kinase domain and were mostly related to the severe clinical phenotype of piebaldism.
CONCLUSION
The new heterozygous c.1982C > T missense mutation on KIT caused piebaldism with café-au-lait macules in this Chinese family. This study provides a new reference index for clinicians to judge the severity of clinical phenotypes of piebaldism, broadens the understanding of the correlation between clinical phenotypes and genotypes of piebaldism, and provides reference of genetic counseling and prenatal diagnosis for affected families.
Topics: Humans; Female; Piebaldism; Proto-Oncogene Proteins c-kit; Cafe-au-Lait Spots; Mutation; Pigmentation Disorders
PubMed: 37357653
DOI: 10.1111/srt.13352 -
BioRxiv : the Preprint Server For... Jan 2024Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting approximately 80% of all human proteins. The human essential X-linked gene, , encodes...
Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting approximately 80% of all human proteins. The human essential X-linked gene, , encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. There is extensive genetic variation in humans with missense, splice-site, and C-terminal frameshift variants in . In mice, is not an essential gene, as there exists a paralogous gene, , that substantially rescues knockout mice from embryonic lethality, whereas double knockouts ( Naa12 are embryonic lethal. However, the phenotypic variability in the mice is nonetheless quite extensive, including piebaldism, skeletal defects, small size, hydrocephaly, hydronephrosis, and neonatal lethality. Here we replicate these phenotypes with new genetic alleles in mice, but we demonstrate their modulation by genetic background and environmental effects. We cannot replicate a prior report of "maternal effect lethality" for heterozygous female mice, but we do observe a small amount of embryonic lethality in the male mice on the inbred genetic background in this different animal facility.
PubMed: 37163119
DOI: 10.1101/2023.04.27.538618 -
Indian Dermatology Online Journal 2023Piebaldism is a rare genetic disorder of congenital leukoderma caused by mutation in proto-oncogene receptor tyrosine kinase. We present a 10-year-old boy with...
Piebaldism is a rare genetic disorder of congenital leukoderma caused by mutation in proto-oncogene receptor tyrosine kinase. We present a 10-year-old boy with congenital depigmented macules suggestive of piebaldism associated with café au lait macules and skin fold freckling complicating the diagnosis. A diagnosis of piebaldism was made via exome sequencing that showed a pathogenic variant of gene with no pathogenic variants of or gene. Our current understanding of the tyrosine kinase function may provide a better explanation into this phenotypic coexistence and does not necessarily represent an overlap with Neurofibromatosis type 1.
PubMed: 37089832
DOI: 10.4103/idoj.idoj_368_22 -
International Journal of Molecular... Feb 2023Adolescence is a critical period of postnatal development characterized by social, emotional, and cognitive changes. These changes are increasingly understood to depend...
Adolescence is a critical period of postnatal development characterized by social, emotional, and cognitive changes. These changes are increasingly understood to depend on white matter development. White matter is highly vulnerable to the effects of injury, including secondary degeneration in regions adjacent to the primary injury site which alters the myelin ultrastructure. However, the impact of such alterations on adolescent white matter maturation is yet to be investigated. To address this, female piebald-virol-glaxo rats underwent partial transection of the optic nerve during early adolescence (postnatal day (PND) 56) with tissue collection two weeks (PND 70) or three months later (PND 140). Axons and myelin in the transmission electron micrographs of tissue adjacent to the injury were classified and measured based on the appearance of the myelin laminae. Injury in adolescence impaired the myelin structure in adulthood, resulting in a lower percentage of axons with compact myelin and a higher percentage of axons with severe myelin decompaction. Myelin thickness did not increase as expected into adulthood after injury and the relationship between the axon diameter and myelin thickness in adulthood was altered. Notably, dysmyelination was not observed 2 weeks postinjury. In conclusion, injury in adolescence altered the developmental trajectory, resulting in impaired myelin maturation when assessed at the ultrastructural level in adulthood.
Topics: Female; Animals; Rats; Myelin Sheath; Axons; Optic Nerve; Optic Nerve Injuries; Demyelinating Diseases
PubMed: 36834755
DOI: 10.3390/ijms24043343 -
Current Biology : CB Feb 2023Reptiles display great diversity in color and pattern, yet much of what we know about vertebrate coloration comes from classic model species such as the mouse and...
Reptiles display great diversity in color and pattern, yet much of what we know about vertebrate coloration comes from classic model species such as the mouse and zebrafish. Captive-bred ball pythons (Python regius) exhibit a remarkable degree of color and pattern variation. Despite the wide range of Mendelian color phenotypes available in the pet trade, ball pythons remain an overlooked species in pigmentation research. Here, we investigate the genetic basis of the recessive piebald phenotype, a pattern defect characterized by patches of unpigmented skin (leucoderma). We performed whole-genome sequencing and used a case-control approach to discover a nonsense mutation in the gene encoding the transcription factor tfec, implicating this gene in the leucodermic patches in ball pythons. We functionally validated tfec in a lizard model (Anolis sagrei) using the gene editing CRISPR/Cas9 system and TEM imaging of skin. Our findings show that reading frame mutations in tfec affect coloration and lead to a loss of iridophores in Anolis, indicating that tfec is required for chromatophore development. This study highlights the value of captive-bred ball pythons as a model species for accelerating discoveries on the genetic basis of vertebrate coloration.
Topics: Animals; Mice; Piebaldism; Zebrafish; Chromatophores; Lizards; Pigmentation; Zebrafish Proteins; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
PubMed: 36702128
DOI: 10.1016/j.cub.2023.01.004 -
Frontiers in Pediatrics 2022We report the case of a girl aged 2 years and 10 months who had fever for 2 days, vomiting, poor mental status for 1 day, and one episode of convulsions.
CASE PRESENTATION
We report the case of a girl aged 2 years and 10 months who had fever for 2 days, vomiting, poor mental status for 1 day, and one episode of convulsions.
SYMPTOMS AND SIGNS
The patient experienced a rapid onset of symptoms with fever, vomiting, and convulsions. Upon physical examination on admission, she presented with the following: temperature 38.6°C; pulse 185 beats/min; respiration 49 beats/min; blood pressure 89/51 mmHg; drowsiness; piebald skin all over her body; rice-grain-sized pustular rashes scattered on the front chest and both lower limbs, protruding from the surface of the skin; bilateral pupils that were equal in size and a circle with a diameter of about 3.0 mm, and slow light reflex; cyanotic lips; shortness of breath; positive for the three-concave sign; a small amount of phlegm that could be heard in both lungs; capillary refill time of 5 s; cold extremities; and a positive Babinski sign.
DIAGNOSTIC METHOD
A chest computed tomography scan showed multiple nodular and flake-like high-density shadows of varying sizes in each lobe in bilateral lungs, and a cavity with blurred edges could be seen in some nodules. A cranial magnetic resonance imaging examination demonstrated that the hyperintensity of diffusion-weighted imaging could be observed on the left cerebellar hemisphere and left parietal blade. Blood cultures, sputum, cerebrospinal fluid, and bronchoalveolar lavage fluid (BALF) by fiberoptic bronchoscopy all indicated the growth of methicillin-resistant (MRSA).
TREATMENT METHODS
After admission, the child was given meropenem combined with vancomycin, cefoperazone sulbactam combined with rifamycin, linezolid (oral) for anti-infection successively, and other adjuvant therapies.
CLINICAL OUTCOMES
The patient recovered clinically and was discharged from our hospital.
RECOMMENDED READERS
Neurology; Respiratory Medicine; Infectious Diseases Department.
PubMed: 36568437
DOI: 10.3389/fped.2022.1045774 -
Genes Nov 2022Albinism is a genetic disorder, present worldwide, caused by mutations in genes affecting melanin production or transport in the skin, hair and eyes. To date, mutations...
Albinism is a genetic disorder, present worldwide, caused by mutations in genes affecting melanin production or transport in the skin, hair and eyes. To date, mutations in at least 20 different genes have been identified. Oculo-cutaneous Albinism type IV (OCA4) is the most frequent form in Asia but has been reported in all populations, including Europeans. Little is known about the genotype-phenotype correlation. We identified two main phenotypes via the analysis of 30 OCA4 patients with a molecularly proven diagnosis. The first, found in 20 patients, is clinically indistinguishable from the classical OCA1 phenotype. The genotype-to-phenotype correlation suggests that this phenotype is associated with homozygous or compound heterozygous nonsense or deletion variants with frameshift leading to translation interruption in the gene. The second phenotype, found in 10 patients, is characterized by very mild hypopigmentation of the hair (light brown or even dark hair) and skin that is similar to the general population. In this group, visual acuity is variable, but it can be subnormal, foveal hypoplasia can be low grade or even normal, and nystagmus may be lacking. These mild to moderate phenotypes are associated with at least one missense mutation in .
Topics: Humans; Piebaldism; Mutation; Mutation, Missense; Phenotype; Genotype
PubMed: 36553465
DOI: 10.3390/genes13122198 -
Frontiers in Medicine 2022Piebaldism is a rare autosomal dominant disease, and roughly 75% patients had gene mutations. Up to date, approximately 90 mutations causing piebaldism were reported.
BACKGROUND
Piebaldism is a rare autosomal dominant disease, and roughly 75% patients had gene mutations. Up to date, approximately 90 mutations causing piebaldism were reported.
METHODS
To identify gene mutations in three pediatric piebaldism patients from different families and explore the genotype-phenotype correlation, peripheral blood DNA were collected from probands and their parents. Whole-exome sequencing was performed to detect potential disease-causing variants in the three probands. Putative variants were validated by Sanger sequencing.
RESULTS
Heterozygous variants of c.2469_2484del (p.Tyr823*), c.1994G > C (p.Pro665Leu), and c.1982_1983insCAT (p.662_663insIle) in gene were detected in three probands. These variants were all novel and classified as pathogenic/likely pathogenic variants according to the interpretation guidelines of American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The probands carrying variants located in tyrosine kinase domain exhibited a more severe phenotype.
CONCLUSION
The piebaldism in three families was caused by novel heterozygous variants. The severity of phenotypes is related with the types and locations of different mutations. Our results further provided evidence for genetic counseling for the three families.
PubMed: 36438053
DOI: 10.3389/fmed.2022.1040747