Expanding the genetic spectrum of giant axonal neuropathy: Two novel variants in Iranian families.

BACKGROUND: Giant axonal neuropathy (GAN) is a progressive childhood hereditary polyneuropathy that affects both the peripheral and central nervous systems. Disease-causing variants in the gigaxonin gene (GAN) cause autosomal recessive giant axonal neuropathy. Facial weakness, nystagmus, scoliosis, kinky or curly hair, pyramidal and cerebellar signs, and sensory and motor axonal neuropathy are the main symptoms of this disorder. Here, we report two novel variants in the GAN gene from two unrelated Iranian families. METHODS: Clinical and imaging data of patients were recorded and evaluated, retrospectively. Whole-exome sequencing (WES) was undertaken in order to detect disease-causing variants in participants. Confirmation of a causative variant in all three patients and their parents was carried out using Sanger sequencing and segregation analysis. In addition, for comparing to our cases, we reviewed all relevant clinical data of previously published cases of GAN between the years 2013-2020. RESULTS: Three patients from two unrelated families were included. Using WES, we identified a novel nonsense variant [NM_022041.3:c.1162del (p.Leu388Ter)], in a 7-year-old boy of family 1, and a likely pathogenic missense variant [NM_022041.3:c.370T>A (p.Phe124Ile)], in two affected siblings of the family 2. Clinical examination revealed typical features of GAN-1 in all three patients, including walking difficulties, ataxic gait, kinky hair, sensory-motor polyneuropathy, and nonspecific neuroimaging abnormalities. Review of 63 previously reported cases of GAN indicated unique kinky hair, gait problem, hyporeflexia/areflexia, and sensory impairment were the most commonly reported clinical features. CONCLUSIONS: One homozygous nonsense variant and one homozygous missense variant in the GAN gene were discovered for the first time in two unrelated Iranian families that expand the mutation spectrum of GAN. Imaging findings are nonspecific, but the electrophysiological study in addition to history is helpful to achieve the diagnosis. The molecular test confirms the diagnosis.

Effects of Medetomidine, Dexmedetomidine and their combination with Acepromazine on the intraocular pressure (IOP), tear secretion and pupil diameter in dogs.

BACKGROUND: A great number of sedatives and anaesthetics have been used to perform surgeries or routine ophthalmologic examinations in animals and sometimes the combination of these medicines has more suitable effects than each one alone. OBJECTIVES: This paper aims to explore the main effects of Medetomidine + Acepromazine, Dexmedetomidine + Acepromazine on intraocular pressure, tear secretion and pupil diameter. METHODS: To accomplish the aforementioned aim, 32 adult dogs (aged one-to-three-years-old) were clinically examined. Dogs were divided into four groups consisting of group DA, Dexmedetomidine (5 µg/kg) + Acepromazine (0.05 mg/kg); Group D, Dexmedetomidine (5 µg/kg); Group M, Medetomidine (10 µg/kg); Group MA, Medetomidine (10 µg/kg) + Acepromazine (0.05 mg/kg). The ocular factors including tear production, pupil diameter and intraocular pressure of both right and left eyes were first measured and then recorded in each dog at time T0 (-15 min). Afterwards, the drugs were administered intramuscularly, based on which the ocular factors were re-measured at T1 (+5 min), T2 (+15 min) and T3 (+20 min). All four groups showed a reduction in intraocular pressure, which was significant in DA, D and M groups. RESULTS: Furthermore, there was a fluctuation in the amount of tear secretion in DA and D groups (increase and then decrease), as well as a significant reduction in M and MA groups. Decreasing in pupil diameter also occurred in all four groups, but the reduction was significant only in DA and MA groups. CONCLUSION: According to the results obtained, as the changes caused by the systemic administration of the above drug compounds did not exceed the physiological range, it can be concluded that these combinations could be utilized as suitable sedatives or pre-anaesthetic compounds in the eye surgeries.

Comparison of sedative and some cardiopulmonary effects of intramuscular medetomidine or medetomidine-tramadol in dogs.

OBJECTIVE: To evaluate the clinical and physiologic effects of intramuscular (IM) administration of medetomidine with and without tramadol in dogs. STUDY DESIGN: Prospective experimental study. ANIMALS: A group of eight mixed breed dogs of both sexes, aged 1-2 years, weighing 16.0 ± 0.6 kg. METHODS: Each dog was studied twice at ≥1 week interval. Medetomidine (5 µg kg-1; treatment M) was administered IM alone or with tramadol (4 mg kg-1; treatment MT). Sedation was scored by a system that included vocalization, posture, appearance, interactive behaviors, resistance to restraint and response to noise. Times from drug administration to ataxia, impaired walking, head drop, sternal and lateral position and standing were recorded. Sedation score, heart rate, respiratory rate, rectal temperature, end-tidal carbon dioxide (Pe'CO2), hemoglobin oxygen saturation and mean noninvasive blood pressure were recorded and compared 15 minutes before and 15, 30 and 45 minutes after drug administration. RESULTS: Dogs administered MT had higher sedation scores than dogs administered M at 30 and 45 minutes after drug administration (p < 0.05). Times to ataxia, impaired walking, head drop and sternal recumbency were not different between the treatments. Time to lateral recumbency was longer in M than in MT (21.1 ± 1.0 versus 17.6 ± 0.7 minutes, respectively; p < 0.05). Time to standing was longer in MT than in M (67.9 ± 1.4 versus 54.5 ± 1.9 minutes, respectively; p < 0.001). Measured physiological variables did not differ between the treatments, with the exception of Pe'CO2, which was higher in MT than in M at all post-treatment evaluation times (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Tramadol combined with medetomidine resulted in greater sedation scores (deeper sedation) than medetomidine alone in dogs, and minimal adverse changes in the physiologic variables were measured.

Assessment of a pan-dermatophyte nested-PCR compared with conventional methods for direct detection and identification of dermatophytosis agents in animals.

Conventional direct microscopy with potassium hydroxide (KOH) and culture were found to lack the ability to establish a fast and specific diagnosis of dermatophytosis. A pan-dermatophyte nested-PCR assay was developed using a novel primer pair targeting the translation elongation factor 1-α (Tef-1α) sequences for direct detection and identification of most veterinary relevant dermatophytes in animal samples suspected to dermatophytosis. A total of 140 animal skin and hair samples were subjected to direct microscopy, culture, and ITS-RFLP/ITS-sequencing of culture isolates for the detection and identification of dermatophytosis agents. Nested-PCR sequencing was performed on all the extracted DNAs using a commercial kit after dissolving the specimens by mechanical beating. Nested-PCR was positive in 90% of samples, followed by direct microscopy (85.7%) and culture (75%). The degree of agreement between nested-PCR and direct microscopy (94.4%) was higher than with culture (83.3%). In 105 culture-positive cases, the measures of agreement for the identification of dermatophytosis agents were as follows: 100% between nested-PCR sequencing and ITS-RFLP/ITS-sequencing and 63.8% between nested-PCR sequencing and culture. The developed nested-PCR was faster as well as more sensitive and specific than conventional methods for detection and identification of dermatophytes in clinical samples, which was particularly suitable for epidemiological studies.

Dermatophytosis due to Microsporum incurvatum: Notification and Identification of a Neglected Pathogenic Species.

A 4-year-old Iranian boy developed erythematous, itchy and annular lesion on his face. Microscopic examination of the scraped samples with 10 % potassium hydroxide (KOH) revealed fungal septate hyphae and arthroconidia. The etiological agent was found to be Microsporum gypseum in mycological examinations. Amplification and restriction digestion of the internal transcribed spacers (ITS) of rDNA was not helpful for identification, but in ITS sequencing the isolate showed 98 % homology to Microsporum incurvatum strain CBS 172.64. Empirical treatment of the patient with griseofulvin for 4 weeks was successful. Other than our isolate, the ITS1 sequences of 38 strains from related species were retrieved from GenBank and phylogenetic tree using maximum likelihood method was constructed. The case isolate clustered apart from other strains of M. incurvatum. Pairwise comparison of ITS1 showed intraspecies variations of 0-13 nucleotides among M. incurvatum strains and an extensive interspecies variation of 33-80 bp and remarkable interspecies size polymorphism between the three sister species in the M. gypseum complex. The high level of ITS1 intraspecific variation is suitable for species identification rather than phylogeographic analysis of M. gypseum complex.