A case study of Duchenne muscular dystrophy caused by Alu element insertion in DMD gene and analysis of its gray-hair symptoms.

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive genetic disorder caused by mutations in the DMD gene, which leads to a deficiency of the dystrophin protein. The main mutation types of this gene include exon deletions and duplications, point mutations, and insertions. These mutations disrupt the normal expression of dystrophin, ultimately leading to the disease. In this study, we reported a case of DMD caused by an insertion mutation in exon 59 (E59) of the DMD gene. The affected child exhibited significant abnormalities in related biochemical markers, early symptoms of DMD, and multiple gray hair. His mother and sister were carriers with slightly abnormal biochemical markers. The mother had mild clinical symptoms, while the sister had no clinical symptoms. Other family members were genetically and physically normal. Sequencing and sequence alignment revealed that the inserted fragment was an Alu element from the AluYa5 subfamily. This insertion produced two stop codons and a polyadenylate (polyA) tail. To understand the impact of this insertion on the DMD gene and its association with clinical symptoms, exonic splicing enhancer (ESE) prediction indicated that the insertion did not affect the splicing of E59. Therefore, we speculated that the insertion sequence would be present in the mRNA sequence of the DMD gene. The two stop codons and polyA tail likely terminate translation, preventing the production of functional dystrophin protein, which may be the mechanism leading to DMD. In addition to typical DMD symptoms, the child also exhibited premature graying of hair. This study reports, for the first time, a case of DMD caused by the insertion of an Alu element into the coding region of the DMD gene. This finding provides clues for studying gene mutations induced by Alu sequence insertion and expands the understanding of DMD gene mutations.

Effects of watercress extract fraction on R-spondin 1-mediated growth of human hair.

OBJECTIVE: Hair loss and greying affect men and women of all ages, often causing psychosocial difficulties. Dickkopf-1 (DKK1), a major hair loss factor secreted from dermal papilla (DP) cells in response to the secretion of dihydrotestosterone (DHT), has been reported to induce and accelerate androgenetic alopecia (AGA). In addition, DKK1 acts as a potent suppressor of melanogenesis and is closely related to hair colour. R-spondin 1 (RSPO1) is a secretory agonist of Wnt signalling known to antagonize the effects of DKK1, including DKK1-mediated hair follicle suppression. In this study, we investigated the effect of watercress extract (WCE) on the secretion of RSPO1 and DKK1 from DP cells as well as its anti-hair loss effect in human hair follicles and patients. METHODS: The in vitro secretion of RSPO1 and DKK1 was measured by ELISA. Human hair follicles were collected from the scalp of a female donor and used for ex vivo organ culture to investigate the effects of WCE on human hair loss. Finally, a 6-month human clinical trial was conducted to examine the effect of WCE-containing lotion on hair growth in a male panel. RESULTS: WCE significantly upregulated RSPO1 secretion and suppressed DKK1 secretion in a dose-dependent manner, even in the presence of DHT. WCE-treated hair follicles elongated 1.6-fold compared with the control, and the level of RSPO1 production in DP as well as RSPO1 bound to the outer root sheath (ORS) increased. In the clinical trial, the hair lotion containing 2% WCE increased hair thickness and density to improve against hair loss symptoms. CONCLUSION: WCE exhibited a strong anti-androgenic effect through its ability to suppress DKK1 secretion and antagonize DKK1 via RSPO1. These findings highlighted the potential use of WCE for the treatment of hair loss.

OBJECTIF: La perte de cheveux et le grisonnement touchent des hommes et des femmes de tous âges, ce qui entraîne souvent des difficultés psychosociales. Selon des rapports, Dickkopf-1 (DKK1), un facteur de perte de cheveux majeur sécrété par les cellules de la papille dermique (PD) en réponse à la sécrétion de dihydrotestostérone (DHT), induit et accélère l'alopécie androgénétique (AAG). En outre, DKK1 agit comme un puissant suppresseur de la mélanogenèse et est étroitement lié à la couleur des cheveux. La protéine R-spondin 1 (RSPO1) est un agoniste sécrétoire de la voie de signalisation Wnt connue pour antagoniser les effets de DKK1, notamment la suppression des follicules pileux médiée par DKK1. Dans cette étude, nous avons étudié l'effet de l'extrait de cresson sur la sécrétion de RSPO1 et de DKK1 à partir des cellules de la PD, ainsi que son effet anti-perte de cheveux sur les follicules pileux humains et chez les patients. MÉTHODES: La sécrétion in vitro de RSPO1 et de DKK1 a été mesurée à l'aide de la méthode ELISA. Des follicules pileux humains ont été prélevés sur le cuir chevelu d'une femme et utilisés pour une culture d'organes ex vivo afin d'étudier les effets de l'extrait de cresson sur la perte de cheveux humains. Enfin, un essai clinique de 6 mois chez l'être humain a été mené pour examiner l'effet d'une lotion contenant de l'extrait de cresson sur la croissance des cheveux au sein d'un panel d'hommes. RÉSULTATS: L'extrait de cresson a significativement régulé à la hausse la sécrétion de RSPO1 et a supprimé la sécrétion de DKK1 de manière dose-dépendante, même en présence de DHT. Les follicules pileux traités avec de l'extrait de cresson ont été multipliés par 1,6 par rapport au groupe témoin, et le niveau de production de RSPO1 dans la PD ainsi que le taux de RSPO1 lié à la gaine externe de la racine ont augmenté. Dans l'essai clinique, la lotion pour cheveux contenant 2 % d'extrait de cresson a augmenté l'épaisseur et la densité des cheveux, améliorant ainsi les symptômes de perte de cheveux. CONCLUSION: La capacité de l'extrait de cresson à supprimer la sécrétion de DKK1 et à antagoniser DKK1 via la protéine RSPO1 lui a conféré un effet anti-androgénique puissant. Ces résultats ont mis en évidence le potentiel de l'extrait de cresson pour le traitement de la perte de cheveux.

Congenital Hypopigmentary Disorders with Multiorgan Impairment: A Case Report and an Overview on Gray Hair Syndromes.

The term congenital hypopigmentary disorders refers to a wide group of heterogeneous hereditary diseases, clinically characterized by inborn pigmentary defects of the iris, hair, and/or skin. They include Gray Hair Syndromes (GHSs), a rare group of autosomal recessive genodermatosis hallmarked by inborn silvery gray hair. GHSs encompass Griscelli, Chediak⁻Higashi, Elejalde, and Cross syndromes, which are all characterized by a broad spectrum of severe multisystem disorders, including neurological, ocular, skeletal, and immune system impairment. In this manuscript, we describe in detail the clinical, trichoscopic, and genetic features of a rare case of Griscelli syndrome; moreover, we provide an overview of all the GHSs known to date. Our report highlights how an accurate clinical examination with noninvasive methods, like trichoscopy, may play a crucial rule in diagnosis of rare and potentially lethal genetic syndromes such as Griscelli syndrome, in which timely diagnosis and therapy may modify the clinical course, quality of life, and likelihood of survival.

[Griscelli syndrome type 3: A new case]. / Syndrome de Griscelli de type 3 : un nouveau cas.

INTRODUCTION: Griscelli syndrome (GS) is a rare autosomal-recessive genetic disease characterized by hypopigmentation of skin and hair. We report a case of GS type 3 with late diagnosis. OBSERVATION: A 31-year-old female patient had presented depigmentation of the hair and eyebrows as well as diffuse skin hypopigmentation during childhood. Microscopic analysis of a hair shaft revealed irregularly distributed clumps of melanin. DNA sequencing showed a homozygous C103T (R35W) transition in exon 1 of MLPH, confirming Griscelli syndrome type 3. DISCUSSION: Three clinical phenotypes of GS have been described based on the underlying genetic defect. GS type 1 and 2 are associated respectively with a central nervous system dysfunction and an immune defect. GS type 3 is an isolated cutaneous form. Diagnosis is confirmed on microscopic examination of hair shafts. 15 cases of GS type 3 have been reported: 9 in males and 6 in females. Mean age at diagnosis is around 12 years. Nine of the reported patients were of Arab origin, four of Turkish origin, and one of Indian origin. R35W mutation was described in 9 cases and E98X and R35Q mutations were each found in one case. CONCLUSION: GS should be suspected in patients presenting gray silvery hair, particularly when these patients are of Arab or Turkish origin.

Association of premature hair graying with family history, smoking, and obesity: a cross-sectional study.

BACKGROUND: Many researchers have been concerned about the association of hair graying with systemic diseases. However, the common factors associated with hair graying and systemic diseases have not been elucidated. OBJECTIVE: This study aimed to identify risk factors for premature hair graying (PHG) in young men. METHODS: We conducted a cross-sectional study using questionnaires in young men. After a pilot study that included 1069 men, we surveyed 6390 men younger than 30 years about their gray hair status and various socioclinical characteristics. RESULTS: The age of participants in the main survey was 20.2 ± 1.3 years (mean ± SD). Of the 6390 participants, 1618 (25.3%) presented with PHG. Family history of PHG (odds ratio [OR], 12.82), obesity (OR, 2.61), and >5 pack-years history of smoking (OR, 1.61) were significantly associated with PHG. In the multivariate analysis, family history of PHG (OR, 2.63) and obesity (OR, 2.22) correlated with the severity of PHG. LIMITATIONS: Owing to the use of questionnaires, the possibility of recall bias exists. Women were not evaluated in this study. CONCLUSION: Smoking, family history of PHG, and obesity are important factors associated with PHG.

[Cutaneous manifestations of cystic fibrosis in an infant: acrodermatitis enteropathica and gray hair]. / Manifestaciones dermatológicas de fibrosis quística en un lactante: acrodermatitis enteropática símil y pelo gris.

INTRODUCTION: Cutaneous manifestations at the time of CF diagnosis are rare. OBJECTIVE: To describe the case of an infant with an unusual cutaneous presentation of cystic fibrosis. CASE REPORT: The case is presented of an infant with delayed physical growth at two months, and at the age of four months, presented with a skin rash and gray hair. Tests revealed the presence of hypoproteinemia and anemia, with the diagnosis of Cystic Fibrosis being confirmed by genetic testing. The rash was completely resolved after pancreatic enzyme replacement therapy. This is the second gray hair case reported in children with this disease. CONCLUSION: Metabolic diseases such as cystic fibrosis should be suspected in malnourished children who develop skin disorders.

Fractal Pattern in the Premature Graying of Hair: A Case Report.

Premature graying of hair (PGH) is a multifactorial condition defined by the graying of hair before the age of 20 in Caucasians and before the age of 30 in African Americans. Although the etiology remains unknown, it has been associated with genetic predisposition, oxidative stress, nutritional deficiencies, and autoimmune diseases. Current treatment options are limited but can include anti-inflammatory medications, vitamins, and hair colorants for symptom control. In this report, we present a case of premature graying in a 32-year-old male, onset at age 15, exhibiting a distinctive fractal pattern. This case represents a unique instance of PGH characterized by an unusual pattern, necessitating further investigation into potential etiological factors and underlying pathophysiological mechanisms.

Elejalde syndrome - A neuroectodermal melanolysosomal disease: A case report.

Background: Elejalde syndrome is a rare neuroectodermal melanolysosomal disease with an autosomal recessive heredity. Patients usually present with silvery-gray hair, neurological abormalities, diffuse skin hypopigmentation and suntanned skin color. Case Presentation: A 3 1/2-year-old boy presented with hemiplegia since the day before admission. Durig hospital admission, he experienced episodes of status epilepticus and loss of consciousness and underwent mechanical ventilation. The patient had silvery-gray hair, consequently the pathologic evaluation of the hair shaft, revealed enlarged irregularly spaced melanin clumps characteristic for silvery-gray hair syndrome. No immunologic dysfunction was detected due to immunological evaluations, subsequently Elejalde syndrome was confirmed. Conclusion: This study adds one new case to the known cases of Elejalde syndrome and confirms that Elejalde patients may not exhibit neurological symptoms until an older age.

Modeling human gray hair by irradiation as a valuable tool to study aspects of tissue aging.

As one of the earliest and most visible phenomenon of aging, gray hair makes it a unique model system for investigating the mechanism of aging. Ionizing radiation successfully induces gray hair in mice, and also provides a venue to establish an organ-cultured human gray hair model. To establish a suitable organ-cultured human gray HF model by IR, which imitates gray hair in the elderly, and to explore the mechanisms behind the model. By detecting growth parameters, melanotic and senescence markers of the model, we found that the model of 5 Gy accords best with features of elderly gray hair. Then, we investigated the formation mechanisms of the model by RNA-sequencing. We demonstrated that the model of organ-cultured gray HFs after 5 Gy irradiation is closest to the older gray HFs. Moreover, the 5 Gy inhibited the expression of TRP-1, Tyr, Pmel17, and MITF in hair bulbs/ORS of HFs. The 5 Gy also significantly induced ectopically pigmented melanocytes and increased the expression of DNA damage and senescence in HFs. Finally, RNA-seq analysis of the model suggested that IR resulted in cell DNA damage, and the accumulation of oxidative stress in the keratinocytes. Oxidative stress and DNA damage caused cell dysfunction and decreased melanin synthesis in the gray HFs. We found that HFs irradiated at 5 Gy successfully constructed an appropriate aging HF model. This may provide a useful model for cost-effective and predictable treatment strategies to human hair graying and the process of aging.

Medication-Induced Repigmentation of Gray Hair: A Systematic Review.

Hair graying is a common sign of aging resulting from complex regulation of melanogenesis. Currently, there is no medical treatment available for hair repigmentation. In this article we review the literature on medication-induced hair repigmentation, discuss the potential mechanisms of action, and review the quality of the literary data. To date, there have been 27 studies discussing medication-induced gray hair repigmentation, including 6 articles on gray hair repigmentation as a primary objective, notably with psoralen treatment or vitamin supplementation, and 21 reports on medication-induced gray hair repigmentation as an incidental finding. Medications noted in the literature include anti-inflammatory medications (thalidomide, lenalidomide, adalimumab, acitretin, etretinate, prednisone, cyclosporin, cisplatinum, interferon-α, and psoralen), stimulators of melanogenesis (latanoprost, erlotinib, imatinib, tamoxifen, and levodopa), vitamins (calcium pantothenate and para-amino benzoic acid), a medication that accumulates in tissues (clofazimine), and a medication with an undetermined mechanism (captopril). Diffuse repigmentation of gray hair can be induced by certain medications that inhibit inflammation or stimulate melanogenesis. There is also low-quality evidence that some vitamin B complex supplementation can promote gray hair darkening. While these compounds are not currently indicated for the treatment of gray hair, their mechanisms shed light on targets for future medications for hair repigmentation.

The Danger of Being Too Sympathetic: Norepinephrine in Alzheimer's Disease and Graying of Hair.

Although alterations in the sympathetic nervous system (SNS) with age have been reported, and serious degenerative diseases of the autonomic nervous system such as multiple system atrophy are more likely to strike older people, connections between dysregulated adrenergic receptors and age-associated diseases and phenotypes have not been well studied. Two recent reports suggest that SNS may be more closely connected than previously appreciated. First, low nanomolar concentrations of Alzheimer's disease (AD)-associated Aß42-amyloid oligomers alter signaling by SNS neurotransmitter norepinephrine (NE) to sufficiently activate kinase GSK3ß to hyperphosphorylate tau, a key mediator of neurotoxicity in AD. Connecting beta-amyloid to tau in AD has been a key quest in understanding AD and developing therapeutics. The α2 adrenergic receptor inhibitory drug idazoxan reduces GSK3ß activity and tau phosphorylation in AD mice with improved cognitive function, even in the presence of beta-amyloid deposits. In this study, SNS activation in the brain coupled with problematic Aß42-amyloid oligomers result in serious consequences that can be ameliorated by reducing SNS signaling. A second example of the detrimental effects of increased SNS signaling is the premature graying of hair in response to stress. Secretion of NE resulting from stress causes differentiation of most hair pigment melanocyte stem cells (MeSCs) into melanocytes, rapidly depleting the hair follicle of pigment-producing cells as mature melanocytes undergo apoptosis and MeSCs are eventually eliminated. Blockade of NE SNS signaling preserves hair coloration in stressed animals. Increased SNS activation has serious apparently irreversible effects on homeostasis in both situations. Although neither report directly addresses aging, given that AD and the loss of hair pigmentation have strong age associations, it is of interest to better understand the role that SNS has in promoting age-associated phenotypes generally and determine if tuning the SNS through drug-mediated attenuation of SNS signaling may be of medical benefit.

Evaluation of Physiological, Psychological, and Lifestyle Factors Associated with Premature Hair Graying.

BACKGROUND: Canities, or hair graying, is believed to be driven by the cytotoxic effect of reactive oxygen species on follicular melanocytes, thus raising the concern that premature hair graying (PHG) may represent an outward sign of systemic oxidative stress. OBJECTIVE: This study aimed to identify the physiological, psychological, and lifestyle factors associated with PHG (defined as graying at age ≤30 years) in men and women. MATERIALS AND METHODS: Data from 467 participants (female = 354 and male = 113; age: 18-77 years) were collected and analyzed, including demographic information, medical history, family history, supplement intake, and lifestyle factors. RESULTS: PHG was found to be significantly associated with a history of PHG in the mother, P<0.001, odds ratio (OR) = 3.165; father, P<0.001, OR = 5.166; maternal grandparent, P= 0.002, OR = 2.442; paternal grandparent, P= 0.007, OR = 2.369; and siblings, P<0.001, OR = 3.125. PHG was significantly associated with iron deficiency (P = 0.026, OR = 1.751) and family history of depression (P = 0.012, OR = 1.603), while herpes simplex virus infection (P = 0.004, OR = 0.367) and smoking history (P = 0.003) demonstrated significant negative associations. In Caucasians only (n = 306), in addition to these trends, irritable bowel syndrome was also significantly associated with PHG (P = 0.010, OR = 2.753). In Asians only (n = 75), history of heart disease in a first-degree relative (P = 0.038) was significantly associated with PHG. LIMITATIONS: As a survey study, the findings may be subject to recall bias. CONCLUSIONS: Important associations exist between PHG and family history of PHG, psychiatric history, supplement use, and vitamin deficiencies, providing insight into the pathophysiology and potential comorbidities of PHG.

Premature Graying of Hair: Review with Updates.

Premature graying of hair (PGH) is defined as graying of hair before the age of 20 years in Caucasians and before 30 years in African American population. It can severely affect the self-esteem of an individual. The exact etiopathogenesis remains unknown, although it has been associated with premature aging disorders, atopy, and autoimmune diseases. Patients, who present with PGH, should be assessed for syndromes and metabolism diseases. Hair dyes remain the main modality of the treatment for cosmetic concerns after nutritional supplementation.

Hair Biology: Growth and Pigmentation.

Healthy hair is vital to identity. Understanding the intricate anatomy and physiology of hair provides insight into the aging process and the eventual loss of either hair pigmentation or hair shafts. Several biologics are available that have enabled altering or slowing the aging process of hair, but, unfortunately, no agent exists that can reverse the natural course. The commonly used biologics are discussed.

Light Microscopy and Polarized Microscopy: A Dermatological Tool to Diagnose Gray Hair Syndromes.

Gray hair syndromes are rare syndromes which have an autosomal recessive inheritance and are characterized by pigmentary dilution of skin and hair, defects in immunological function, and nervous system defects. They comprise three disorders namely Chediak-Higashi syndrome (CHS), Griscelli syndrome (GPS), and Elejalde syndrome. Clinically, it is difficult to distinguish these disorders as their clinical features may overlap. Hence, to make a correct diagnosis and differentiate between CHS and GPS light microscopic examination of skin and hair shafts as well as peripheral blood smear evaluations should be done. In cases where the diagnosis is not possible chromosomal analysis for specific mutations can be done. In resource-poor settings where chromosomal analysis is not possible, and light microscopy findings are inconclusive, polarized microscopy can serve as a useful tool to distinguish between CHS and GPS. We report three cases with gray hair syndromes where the diagnosis on light microscopy and polarized microscopy of hair shaft correlated with the bone marrow examination findings and chromosomal analysis, thus emphasizing the importance of a noninvasive, cost-effective, and time-saving alternative in the diagnosis of these syndromes.

Age Estimation Based on Appearance of Gray Hair in Different Body Sites of Sri Lankan Autopsy Cases.

Owing to the scanty evidence on usefulness of information of appearance of gray hair for age estimation, this study was conducted to estimate age based on the appearance of gray hair on different body sites in a sample of autopsy cases in Sri Lanka. A descriptive cross-sectional study was conducted in Teaching Hospital-Kurunegala during 2011 to 2013. Based on the pattern of the presence of gray hair in different body sites, six stages of gray hair were computed. The analysis 1155 autopsy cases revealed strong, positive correlations between age and appearance of gray hair in head, mustache, beard, and pubic area among males and strong, positive correlations between age and the appearance of gray hair in head and pubic area among females (p < 0.01). Our findings demonstrate the value of information of appearance of gray hair for age estimation in the field of forensic science.

Griscelli syndrome type-3.

Griscelli syndrome (GS) is a rare autosomal recessive multisystem disorder of pigmentary dilution of skin, silver gray hair, variable immunodeficiency, neurological impairment, and abnormal accumulation of melanosomes in melanocytes. GS type 3 is characterized by hypomelanosis with no immunological and neurological manifestation. Prognosis is very good in type 3 GS and usually require no active intervention, as opposed to type 1 and 2 where early diagnosis and treatment plays a crucial role in patient's survival. The characteristic phenotypic appearance, especially the pigment dilution of the patient's hair, is emphasized here.

Efficacy and Safety of Pueraria lobata Extract in Gray Hair Prevention: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Graying of hair-a sign of aging-raises cosmetic concerns. Individuals with gray hair often look older than others their age; therefore, some dye their hair for aesthetic purposes. However, hair colorants can induce many problems including skin irritation, allergic reaction and hair-breakage. OBJECTIVE: This randomized, double-blind clinical trial was performed in order to examine the effects of APHG-1001, a compound including an extract from Pueraria lobata, on graying hair. METHODS: A total of 44 female subjects were randomly treated with either APHG-1001 or placebo twice daily for 24 weeks. Using the phototrichogram analysis, a count of newly developed gray hair was estimated. Investigator assessment and subject self-assessment were also performed in order to evaluate the efficacy of the compound. RESULTS: The mean number of newly developed gray hair at 24 weeks was 6.3/cm(2) in the APHG-1001 group and 11.4/cm(2) in the placebo group; the difference was statistically significant (p<0.05). However, the investigator assessment and subject self-assessment did not show any significant change in the gross appearance of hair grayness by the end of the study. No severe adverse events in either group were observed. Moreover, the incidence of adverse events did not differ between the groups. CONCLUSION: This clinical trial revealed that APHG-1001, which contains an extract of P. lobata, could prevent the development of new gray hair without any remarkable adverse effects. Thus, it can be considered as a viable treatment option for the prevention of gray hair.

A survey of the awareness, knowledge and behavior of hair dye use in a korean population with gray hair.

BACKGROUND: Gray hair naturally develops in the process of human aging. Many people with gray hair periodically dye their hair. Hair dyeing products are widely used and they can cause adverse effects. Therefore, the user's knowledge and recognition about hair dyeing and related side effects are important. OBJECTIVE: The goal of this study was to lay the foundation for understanding, preventing and treating side effects caused by hair coloring products. METHODS: We conducted a questionnaire survey for adult males and females aged over 20 who had gray hair. A total of 500 subjects were included in this study and statistical analysis was performed. RESULTS: Large numbers of the people who had experience with hair dye (233 out of 319 people, 73.0%) did not know about the exact brand name of the hair dye product that they were using. Of 319 hair dye users, 23.8% (76 out of 319) people stated that they experienced side effects. Despite the occurrence of side effects from hair dyeing products, it seems they did not realize the seriousness of the side effects or the need for treatment. CONCLUSION: It is advisable to introduce a system that enables users to become aware of the ingredients and side effects of hair coloring products and give opportunities for users to become aware of the side effects of hair coloring through education, publicity and publication of an informational booklet.