Solar radiation leads to increased collagenase gene expression (MMP1) in HERDA (Hereditary equine regional dermal asthenia) affected horses and may explain the typical dorsal distribution of their lesions.

BACKGROUND: Hereditary equine regional dermal asthenia (HERDA) is a genetic disease that alters collagen biosynthesis. Affected horses exhibit fragile, hyperextensible skin, especially over the dorsal region. Although ultraviolet (UV) radiation seems to contribute to the regional distribution of lesions and worsening of clinical signs, the molecular mechanisms involved are largely unknown. OBJECTIVES: To evaluate the effect of solar radiation on matrix metalloproteinase MMP1, MMP8 and MMP13 gene expression in the dorsal and ventral skin of HERDA-affected and HERDA-unaffected horses [wild-type (WT) horses]. ANIMALS: Six HERDA-affected and six unaffected Quarter horses (WT) were paired according to age, sex and coat colour. MATERIALS AND METHODS: Horses were submitted to 30 day sunlight restriction, followed by 15 day sunlight exposure. Dorsal and ventral skin biopsies were obtained at six sampling times over 45 days. The expression of MMP1, MMP8 and MMP13 genes was measured by quantitative PCR. RESULTS: Although solar radiation modulated MMP1, MMP8 and MMP13 expression, the effects were more pronounced on MMP1. Sun exposure for three days significantly upregulated MMP1 in the dorsal region when compared to the ventral skin in both unaffected and HERDA-affected horses. CONCLUSIONS AND CLINICAL RELEVANCE: This study shows that solar irradiation leads to upregulation of skin collagenase genes particularly MMP1 in the dorsal, sun-exposed skin of horses. Furthermore, this was more marked in HERDA-affected horses. The increased activity of collagenases on the disorganised collagen present in HERDA affected horses would explain why UV radiation leads to deterioration of clinical signs in affected individuals.

Relevance of CYP3A4*20, UGT1A1*37 and UGT1A1*28 variants in irinotecan-induced severe toxicity.

Severe irinotecan-induced toxicity is associated with UGT1A1 polymorphisms. However, some patients develop side-effects despite harbouring a normal UGT1A1 genotype. As CYP3A4 is also an irinotecan-metabolizing enzyme, our study aimed to elucidate the influence of the CYP3A4*20 loss-of-function allele in the toxicity profile of these patients. Three-hundred and eight metastatic colorectal cancer patients treated with an irinotecan-containing chemotherapy were studied. The presence of CYP3A4*20, UGT1A1*37 and UGT1A1*28 alleles was tested. Associations between these genetic variants and toxicity were evaluated. UGT1A1*28 was significantly associated with severe diarrhoea, neutropenia and asthenia (P = 0.002, P = 0.037 and P = 0.041, respectively). One patient with the UGT1A1*28/*37 genotype presented with grade IV neutropenia and lethal septic shock. One heterozygous UGT1A1 (*1/*28) patient also carried the CYP3A4*20 allele but did not develop toxicity. We confirm that UGT1A1*37 and UGT1A1*28 are associated with severe toxicity and suggest that the CYP3A4*20 allele does not play a role in irinotecan-induced toxicity.

Exposició a tuberculosi pulmonar en una unitat neonatal: decisions diagnòstiques i terapèutiques / Exposición a tuberculosis pulmonar en una unidad neonatal: decisiones diagnósticas y terapéuticas / Exposure to pulmonary tuberculosis in a neonatal unit: diagnostic and therapeutic decisions

Fonament: els nounats tenen un risc incrementat de patir malaltia tuberculosa greu a causa de la seva condició d'immunosupressió. Objectiu: avaluar la incidència d'infecció tuberculosa o malaltia latent en una cohort de nounats exposats a un treballador sanitari d'una unitat neonatal diagnosticat de malaltia tuberculosa pulmonar, així com descriure les estratègies per al seu diagnòstic i tractament. Mètode: per al cribratge inicial es va fer una prova de tuberculina (PT) i una radiografia (Rx) toràcica. En cas de dubte, es practicaria una tomografia axial computada (TC) i un QuantiFERON(R)-TB Gold test. Descartada la infecció, es va iniciar tractament amb isoniazida fins als 6 mesos. A aquesta edat, es va fer una segona PT. Resultats: seixanta nounats van estar exposats al cas índex. La PT va ser negativa tant a l'inici com als 6 mesos. Un nadó presentava una imatge dubtosa en la radiografia toràcica, però la TC i el QuantiFERON(R)-TB Gold test van ser normals. El 88,6% dels nounats van iniciar profilaxi, es va contraindicar en el 3% i hi va haver negativa dels pares en el 8%. Tan sols un pacient va presentar efectes secundaris per isoniazida. El 78% dels casos va completar la profilaxi. Als 12 mesos no es va detectar cap cas de tuberculosi. Conclusions: la incidència d'infecció tuberculosa en nounats hospitalitzats exposats és baixa, però, a causa de la gravetat potencial, la profilaxi amb isoniazida fins als 6 mesos i un cribratge precoç amb una PT i una Rx toràcica poden ser una estratègia vàlida per minimitzar el risc

Fundamento. Los neonatos tienen un riesgo incrementado de sufrir enfermedad tuberculosa grave dada su condición de inmunosupresión. Objetivo. Evaluar la incidencia de infección tuberculosa o enfermedad latente en una cohorte de neonatos expuestos a un trabajador sanitario de una unidad neonatal diagnosticado de enfermedad tuberculosa pulmonar, así como describir las estrategias para su diagnóstico y tratamiento. Método. Para el cribado inicial se realizó una prueba de tuberculina (PT) yuna radiografía (Rx) torácica. En caso de duda, se practicaría tomografía axial computerizada (TC) y prueba del QuantiFERON®-TB Gold test. Descartada la infección, se inició tratamiento con isoniazida hasta los 6 meses. A esta edad se practicó una segunda PT. Resultados. Sesenta neonatos fueron expuestos. La PT fue negativa tanto al inicio como a los 6 meses. Un neonato presentaba una imagen dudosa en la radiografía torácica, pero la TC y el QuantiFERON®-TB Gold test fueron normales. El 88,6% de los neonatos iniciaron profilaxis, se contraindicó en el 3% y hubo negativa de los padres en el 8%. Tan sólo un paciente presentó efectos secundarios por isoniazida. El 78% de los casos completó la profilaxis. A los 12 meses no se detectó ningún caso de tuberculosis. Conclusiones. La incidencia de infección tuberculosa en neonatos hospitalizados expuestos es baja, pero, debido a la potencial gravedad, la profilaxis con isoniazida hasta los 6 meses y un cribado precoz con una PT y una Rx torácica pueden ser una estrategia válida para minimizar el riesgo (AU)

Background. Neonates have an increased risk to suffer severe tuber culosis due to their immunosuppressed condition. Objective. To assess the incidence of tuberculosis infection or latent disease in a cohort of newborns exposed to a healthcare worker of the neonatal unit, diagnosed with pulmonary tuberculosis disease, as well as describe diagnostic and treatment strategies. Method. Tuberculin skin test (TST) and chest X-rays were performed at the initial screening. Chest computed tomography (CT) and QuantiFERON®-TB Gold test were performed on cases where chest X-ray was not clear. Once all diagnostic tests were negative, infants were treated with isoniazid up to 6 months of age. At this age, a second TST was performed. Results. 60 newborns were exposed. TST were negative at baseline and at 6 months. One infant had an abnormal chest X-ray, with normal findings on CT and QuantiFERON®-TB Gold test. 88.6% neonates started with prophylaxis, it was contraindicated in 3% and was refused by the parents in 8%. Isoniazid was withdrawn due to side effects in only 1 infant. Prophylaxis was completed by 78% of patients. At 12 months, no cases of tuberculosis were reported. Conclusions. The tuberculous infection incidence in hospitalized neonates exposed is low but, due to the potential severity, prophylaxis with isoniazid until 6 months and an early screening with TST and chest X-ray is a valid strategy to minimized risks (AU)

Influences of AMY1 gene copy number and protein expression on salivary alpha-amylase activity before and after citric acid stimulation in splenic asthenia children.

OBJECTIVE: To compare the correlations between salivary alpha-amylase (sAA) activity and amylase, alpha 1 (salivary) gene (AMYl) copy number or its gene expression between splenic asthenia and healthy children, and investigate the reasons of attenuated sAA activity ratio before and after citric acid stimulation in splenic asthenia children. METHODS: Saliva samples from 20 splenic asthenia children and 29 healthy children were collected before and after citric acid stimulation. AMYl copy number, sAA activity, and total sAA and glycosylated sAA contents were determined, and their correlations were analyzed. RESULTS: Although splenic asthenia and healthy children had no differences in AMY1 copy number, splenic asthenia children had positive correlations between AMY1 copy number and sAA activity before or after citric acid stimulation. Splenic asthenia children had a higher sAA glycosylated proportion ratio and glycosylated sAA content ratio, while their total sAA content ratio and sAA activity ratio were lower compared with healthy children. The glycosylated sAA content ratio was higher than the total sAA content ratio in both groups. Splenic asthenia and healthy children had positive correlations between total sAA or glycosylated sAA content and sAA activity. However, the role played by glycosylated sAA content in sAA activity in healthy children increased after citric acid stimulation, while it decreased in splenic asthenia children. CONCLUSION: Genetic factors like AMY1 copy number variations, and more importantly, sAA glycosylation abnormalities leading to attenuated sAA activity after citric acid stimulation, which were the main reasons of the attenuated sAA activity ratio in splenic asthenia children compared with healthy children.

Ocular dimensions, corneal thickness, and corneal curvature in quarter horses with hereditary equine regional dermal asthenia.

OBJECTIVES: The aim of this study was to compare ocular dimensions, corneal curvature, and corneal thickness between horses affected with hereditary equine regional dermal asthenia (HERDA) and unaffected horses. ANIMALS: Five HERDA-affected quarter horses and five healthy control quarter horses were used. METHODS: Schirmer's tear test, tonometry, and corneal diameter measurements were performed in both eyes of all horses prior to ophthalmologic examinations. Ultrasonic pachymetry was performed to measure the central, temporal, nasal, dorsal, and ventral corneal thicknesses in all horses. B-mode ultrasound scanning was performed on both eyes of each horse to determine the dimensions of the ocular structures and to calculate the corneal curvature. RESULTS: Each corneal region examined in this study was thinner in the affected group compared with the healthy control group. However, significant differences in corneal thickness were only observed for the central and dorsal regions. HERDA-affected horses exhibited significant increases in corneal curvature and corneal diameter compared with unaffected animals. The ophthalmologic examinations revealed mild corneal opacity in one eye of one affected horse and in both eyes of three affected horses. No significant between-group differences were observed for Schirmer's tear test, intraocular pressure, or ocular dimensions. CONCLUSIONS: Hereditary equine regional dermal asthenia-affected horses exhibit decreased corneal thickness in several regions of the cornea, increased corneal curvature, increased corneal diameter, and mild corneal opacity. Additional research is required to determine whether the increased corneal curvature significantly impacts the visual accuracy of horses with HERDA.

Dermatological and morphological findings in quarter horses with hereditary equine regional dermal asthenia.

BACKGROUND: Hereditary equine regional dermal asthenia (HERDA) is an autosomal recessive disorder affecting quarter horses (QHs); affected horses exhibit characteristic skin abnormalities related to abnormal collagen biosynthesis. HYPOTHESIS/OBJECTIVES: To characterize the thickness and morphological abnormalities of the skin of HERDA-affected horses and to determine the interobserver agreement and the diagnostic accuracy of histopathological examination of skin biopsies from horses with HERDA. ANIMALS: Six affected QHs, confirmed by DNA testing, from a research herd and five unaffected QHs from a stud farm. METHODS: The skin thickness in 25 distinct body regions was measured on both sides in all affected and unaffected horses. Histopathological and ultrastructural evaluation of skin biopsies was performed. RESULTS: The average skin thickness in all of the evaluated regions was thinner in the affected horses. A statistically significant difference between skin thickness of the affected and unaffected animals was observed only when the average magnitude of difference was ≥38.7% (P = 0.038). The interobserver agreement for the histopathological evaluation was fair to substantial. The histopathological sensitivity for the diagnosis of HERDA was dependent on the evaluator and ranged from 73 to 88%, whereas the specificity was affected by the region sampled and ranged from 35 to 75%. CONCLUSIONS AND CLINICAL IMPORTANCE: Despite the regional pattern of the cutaneous signs, skin with decreased thickness was not regionally distributed in the HERDA-affected horses. Histopathological evaluation is informative but not conclusive for establishing the diagnosis. Samples of skin from the neck, croup or back are useful for diagnosis of HERDA. However, the final diagnosis must be confirmed using molecular testing.

Allele frequency of hereditary equine regional dermal asthenia in American Quarter horses in Brazil determined by quantitative real-time PCR with high resolution melting analysis.

Hereditary equine regional dermal asthenia (HERDA) is a genetic disorder that occurs in the American Quarter horse (AQH) and is caused by a c.115G>A missense mutation in the peptidylprolyl isomerase B (PPIB) gene. Using a quantitative real-time PCR high resolution melting analysis genotyping assay for the PPIB mutation, the estimated HERDA allele and carrier frequencies in a sample of Brazilian AQHs were 2.9% and 5.8%, respectively.

Heritable equine regional dermal asthenia.

Hereditary equine regional dermal asthenia is a form of Ehlers-Danlos syndrome, and has an autosomal recessive mode of inheritance. Affected horses are typically born normal and develop lesions within the first 2 years of life. The most common symptoms of the disease include stretchy, loose skin that feels doughy or mushy. More severely affected horses experience spontaneous skin sloughing and extensive lacerations, hematomas, and seromas from minor trauma. Affected horses have a higher than expected incidence of corneal ulcers. DNA testing can normal, establish carrier and affected status. Palliative therapy is available, but no curative treatment exists.

[Effect of euodiae fructus on hepatic energy metabolism-related mechanisms of reserpine-induced asthenia cold syndrome rats].

OBJECTIVE: To discuss the effect of Euodiae Fructus on hepatic energy metabolism-related mechanisms of mitochondria of hepatic tissues of asthenia cold syndrome rats. METHOD: Rats were subcutaneously injected with Reserpine to establish the model. After the oral administration with Euodiae Fructus for 12 d, the oxygen electrode method was adopted to determine the respiration efficiency. The expressions of Cox4, Atp5b, Ucp2,Pgc-1alpha, Nrf1, Tfam mRNA were assayed by using RT-PCR method. RESULT: Euodiae Fructus 4.2 g x kg(-1) could obviously increase ST3 and RCR of asthenia cold syndrome rats, and expressions of Cox4, Ucp2 Nrf1 mRNA. It could also increase expressions of Atp5b and Pgc-1alpha mRNA, but with no statistical significance. No obvious change was observed in Tfam mRNA expression. Euodiae Fructus 4.2 g x kg(-1) could significantly increase ST3 and RCR of asthenia cold syndrome rats and Pgc-1alpha mRNA and Nrf1 mRNA expressions, and significantly decrease P/O, with no obvious impact on Cox4, AtpSb, Ucp2, Tfam mRNA expressions. CONCLUSION: Euodiae Fructus can promote mitochondrial respiratory function and oxidative phosphorylation efficiency by improving Pgc-1alpha mRNA and Nrf1 mRNA expressions and regulating Cox4 and Atp5b mRNA in mitochondrial respiratory chain. It can also strengthen mitochondrial uncoupling respiration and add heat production by activating Ucp2 mRNA expression in liver.

[Influence of Aconiti Lateralis Radix Praeparata on asthenia cold syndrome rats with whole genome gene expression of liver by gene chip technique].

OBJECTIVE: To study the influence of Aconiti Lateralis Radix Praeparata on asthenia cold syndrome rats with whole genome gene expression of liver by gene chip technique. METHOD: The asthenia cold syndrome rat models were established by administering traditional Chinese medicine raw Gypsum Fibrosum, Gentianae Radix, Phellodendri Chinensis Cortex and Anemarrhenae Rhizoma. After treated with Aconiti Lateralis Radix Praeparata, the rats' liver gene expressions were detected using gene chip. Differential expression genes were screened for gene function annotation, and some genes were selected to check the accuracy of the results by RT-PCR. RESULT: Compared with the asthenia cold model group, the asthenia cold treatment group showed 212 differential expression genes, mainly involving function of immune response and oxidoreductase activity. CONCLUSION: Aconiti Lateralis Radix Praeparata is proved to have an effect on up-regulating immune response-related genes and oxidizing oxidoreductase activity-related genes of asthenia cold syndrome rats and may be a molecular mechanism for classical warm-nature medicine Aconiti Lateralis Radix Praeparata in warming meridians and dissipating cold.

Sunitinib-induced asthenia: from molecular basis to clinical relief.

Asthenia-fatigue syndrome (AFS) is defined as a persistent, subjective sense of tiredness related to cancer or its treatment and greatly impacts quality of life among cancer patients. All tyrosine kinase inhibitors, but especially sunitinib, may induce AFS. The reason for sunitinib-induced AFS is not yet well understood. Adverse events caused by sunitinib associated with AFS may include anemia, hypothyroidism, nausea and vomiting. However, AFS is also reported when active treatment with sunitinib is ongoing, and no other relevant adverse event can justify it. The molecular mechanisms by which sunitinib triggers AFS remain elusive. Sunitinib displays multiple off-target tyrosine-kinase interactions and competitively inhibits multiple proteins through the blockade of their ATP-binding sites. The broad spectrum of kinases inhibited may play a key role not only in terms of activity but also in terms of toxicity induced by sunitinib. This study considered different clinical observations and current metabolic and pharmacological knowledge, leading to hypotheses regarding which molecular mechanisms may be involved in sunitinib-induced AFS in cancer patients. Deeper knowledge of the molecular mode of action of sunitinib may lead to improved optimization of its clinical use.

Cutaneous asthenia in a Warmblood foal.

A 6-week-old Warmblood colt foal was presented for investigation of multiple haematoma formation in various locations, poor wound healing and abnormal scar formation. Based on the history and clinical presentation of hyperextensible skin with prolonged skin tenting, the foal was diagnosed with cutaneous asthenia and euthanased because of the poor prognosis. Histopathological and electron microscopic findings were inconclusive. This is the first case report of cutaneous asthenia in a Warmblood horse in Australia. Cutaneous asthenia is reviewed with particular reference to hereditary equine regional dermal asthenia and its similarities and differences to the case presented.

Prevalence of the mutation in cyclophilin B (PPIB), a causal candidate gene for HERDA, among Quarter Horses in France.

Hereditary equine regional dermal asthenia (HERDA) in Quarter Horses is an inherited degenerative skin disease. Initially reported as hyperelastosis cutis, HERDA has a phenotype of hyperextensible, fragile skin, with secondary seromas, haematomas, ulcers and scarring. It primarily affects the dorsal aspect of the body. An autosomal recessive mode of inheritance is considered likely, with affected horses more at risk to produce affected offspring. A mutation in cyclophilin B (PPIB) as a novel, causal candidate gene for HERDA has been described, and verified as segregating with carriers and affected horses. Screening of control Quarter Horses in the USA has indicated a 3.5% carrier frequency. The prevalence of this mutation among Quarter Horses in France was determined to be 1.6%.

Ocular findings in Quarter Horses with hereditary equine regional dermal asthenia.

OBJECTIVE: To compare ocular structures of Quarter Horses homozygous for hereditary equine regional dermal asthenia (HERDA) with those of Quarter Horses not affected by HERDA (control horses) and to determine the frequency of new corneal ulcers for horses with and without HERDA during a 4-year period. DESIGN: Cohort study of ocular structures and retrospective case series of horses with and without HERDA. ANIMALS: The cohort portion of the study involved 10 Quarter Horses with HERDA and 10 Quarter Horses without HERDA; the retrospective case series involved 28 horses with HERDA and 291 horses without HERDA. PROCEDURES: Ophthalmic examinations, Schirmer tear tests, tonometry, corneal pachymetry, histologic examinations, and scanning electron microscopy (SEM) were performed in cohorts of Quarter Horses with and without HERDA. Records were reviewed to determine the incidence of corneal ulcers in horses with and without HERDA during a 4-year period. RESULTS: Corneal thickness of horses with HERDA was significantly less than that of control horses, but tear production of horses with HERDA was significantly greater than that of control horses. Results of SEM revealed zones of disorganized, haphazardly arranged collagen fibrils in corneas of horses with HERDA that were not evident in corneas of control horses. The incidence of corneal ulcers was significantly greater for horses with HERDA than for horses without HERDA during the 4-year period. CONCLUSIONS AND CLINICAL RELEVANCE: Alterations in corneal thickness, arrangement of collagen fibers, and incidence of corneal ulcers indicated that abnormalities in horses with HERDA were not limited to the skin.

[Swiss warmblood horse with symptoms of hereditary equine regional dermal asthenia without mutation in the cyclophylin B gene (PPIB)]. / Schweizer Warmblutfohlen mit Symptomen von hereditärer dermaler Asthenie (HERDA) ohne Mutation im Cyclophilin B-Gen (PPIB).

Hereditary equine dermal asthenia (HERDA) is an autosomal recessive skin disease that affects predominantly Quarter Horses and related breeds. Typical symptoms are easy bruising and hyperextensible skin on the back. The prognosis is guarded, as affected horses cannot be ridden normally and are often euthanised. In the Quarter Horse, HERDA is associated with a mutation in cyclophilin B (PPIB), an enzyme involved in triple helix formation of collagen. Here we describe the case of a Swiss Warmblood filly with symptoms of HERDA without PPIB-mutation and in which we also could exclude Ehlers-Danlos syndrome Type IV, VI, VIIA, VIIB and VIIC (dermatosparaxis type) as etiological diseases.

[Imerslund-Gräsbeck syndrome]. / Maladie d'Imerslund-Gräsbeck.

Anemia is a very common symptom encountered in numerous clinical situations in pediatrics. Etiologies range from classic iron-deficiency anemia to the more particular etiologies. We report on a clinical history where usual symptoms such as asthenia, drowsiness and proteinuria provided a rare diagnosis: Imerslund-Gräsbeck syndrome. We discuss the exams to be done with aregenerative macrocytic anemia so as not to underestimate these diagnoses, which each require adapted treatments.

[Gene chip study on cerebral gene of effect of Jinkui Shenqiwan and Youguiwan on mouse model of kidney-yang asthenia with syndrome disproved according to therapeutic efficacy of drugs used].

OBJECTIVE: To inquire into the cerebral gene change of effect of Jingui Shenqiwan and Youguiwan for animal model of kidney-yang asthenia caused by excessive physical and sexual activities, which may study the effect mechanism of the medicine with syndrome disproved therapeutic efficacy of drugs used. METHOD: Male mice of Kunming species, weight 35-40 g, and female weight 28-35 g were randomly divided into four groups: control group, model group and treatment groups of Jigui Shenqiwan and Youguiwan in which there were ten male mice, fifteen ones, ten ones and ten ones, respectively. All of them were fed normally, and poured into their stomach with 0.5 mL of distill water for each mouse in the control group and model group, and with 0.5 mL suspension of the drugs (including 1.1 g x kg(-1) drug) for each one in the treatment groups every day. The mice in the model group and treatment groups were kept by means of each male mouse with six female mice in the same cage, and all male mice swam until they gradully submerged and were scooped up from water once everyday for lasting four weeks to induce the kidney-yang asthenia with excessive physical and sexual activities. Animals' manifestation such as fearing cold, activity and responses, mouse' fur and so on were observed. The brain gene were detected with the mouse brain gene chip of 36K Mouse genome array made by Capital Bio Corp. Beijing, China, and the differential expression gene were screened according to the ratio equal to or above 2 and equal to or below 0.5 with the related fluorescent intensity comparing the two groups, which could be further verified in the light of partly differential expression gene with qRT-PCR. RESULT: The mouse model of kidney-yang asthenia in the model group was successfully induced by way of excessive physical and sexual activities. There were twenty-three genes among up-regulated genes in the model group versus control group but down-regulated genes in the treatment groups versus model group, chiefly including the genes association with inflammation/immunization, neurotransmissions/ signal transduction and so on. There were six genes among the down-regulated genes in the model group versus control group but upregulated in the treatment groups versus model group, mainly involving the related genes of cellular cycle and structure, neurotransmissions/signal transduction, transcription and et al. CONCLUSION: Jigui Shenqiwan and Youguiwan may make it markedly up-regulated to notably down-regulated genes of hormone and melanin-concentrating hormone (MCH) for model of mouse of kidney-yang asthenia, and promote cellular proliferation, which can inquire into effect mechanism of the drug in genetic level at the same time.

Evaluation of allele frequencies of inherited disease genes in subgroups of American Quarter Horses.

OBJECTIVE: To estimate allele frequencies of the hyperkalaemic periodic paralysis (HYPP), lethal white foal syndrome (LWFS), glycogen branching enzyme deficiency (GBED), hereditary equine regional dermal asthenia (HERDA), and type 1 polysaccharide storage myopathy (PSSM) genes in elite performance subgroups of American Quarter Horses (AQHs). DESIGN: Prospective genetic survey. ANIMALS: 651 elite performance AQHs, 200 control AQHs, and 180 control American Paint Horses (APHs). PROCEDURES: Elite performance AQHs successful in 7 competitive disciplines (barrel racing, cutting, halter, racing, reining, western pleasure, and working cow horse) were geno- typed for 5 disease-causing alleles. Age-matched control AQHs and APHs were used to establish comparative whole-breed estimates of allele frequencies. RESULTS: Highest allele frequencies among control AQHs were for type 1 PSSM (0.055) and GBED (0.054), whereas HERDA (0.021) and HYPP (0.008) were less prevalent. Control APHs uniquely harbored LWFS (0.107) and had high prevalence of HYPP (0.025), relative to AQHs. Halter horse subgroups had significantly greater allele frequencies for HYPP (0.299) and PSSM (0.155). Glycogen branching enzyme deficiency, HERDA, and PSSM were found broadly throughout subgroups; cutting subgroups were distinct for HERDA (0.142), and western pleasure subgroups were distinct for GBED (0.132). Racing and barrel racing subgroups had the lowest frequencies of the 5 disease genes. CONCLUSIONS AND CLINICAL RELEVANCE: Accurate estimates of disease-causing alleles in AQHs and APHs may guide use of diagnostic genetic testing, aid management of genetic diseases, and help minimize production of affected foals.