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Molecular Genetic Diagnosis of Human Malignant Hyperthermia
Published in S. Tsuyoshi Ohnishi, Tomoko Ohnishi, Malignant Hyperthermia, 1994
Autosomal recessive inheritance arises in the offspring of two phenotypically normal heterozygotes. The disease is often confined to a single sibship rather than in multiple generations, and females and males are equally affected. Autosomal recessive MH predisposition has been described, but always in conjunction with other phenotypic features. Deficiency of carnitine palmitoyl transferase II (on chromosome 1), the enzyme that liberates Jong chain fatty acids on the inner mitochondrial membrane, is associated with rhabdomyolysis and MH-like episodes during anesthesia with trigger agents.34 A positive contracture test has been reported in Brody myopathy, a deficiency of Ca2+ ATPase (on chromosome 12) responsible for sequestering unbound ionized calcium in the SR.35 In both of these MH-related diseases the fundamental defect can be traced to deficient activity of a catalytic enzyme in common with many autosomal recessive disorders. Because pairs of mutant alleles are required at the same locus to manifest the disease phenotype, consanguinity is more prevalent in recessive inheritance. The mating of an individual homozygous for a recessive trait to a heterozygote will on average produce a 50/50 distribution of affected children. Termed pseudodominance, this union must be distinguished from autosomal dominant inheritance by wider scrutiny of the affected pedigree. Because many recessive disorders are sporadic, and family history may not be contributory, the frequency of the mutant allele and new mutation rate in the population are critical variables in estimating recurrence risk of recessive disorders.
Genetic testing for inherited ocular conditions in a developing country
Published in Ophthalmic Genetics, 2020
Mario Zanolli, Joaquín I. Oporto, Juan I. Verdaguer, Juan Pablo López, Sergio Zacharías, Pablo Romero, Diego Ossandón, Oliver Denk, Olga Acuña, José Manuel López, Ricardo Stevenson, Bernardita Álamos, Hernán Iturriaga
Patient 1 was a 36-year-old asymptomatic woman who was evaluated for LASIK surgery. She had no family history of retinal disorders or any previous relevant medical condition. Her best-corrected visual acuity (BCVA) was 20/20 in both eyes. Ophthalmoscopy revealed a pericentric ring atrophy in the midperiphery, which was concordant with the optical coherence tomography (OCT) and Goldmann perimetry results. Work-up, which included audiometry, revealed subclinical hypoacusia. A retinal dystrophy panel revealed a compound heterozygous mutation in the USH2A gene (c.4377A>G c.1550 + 16 T > C). Over the next 2 years, she developed nyctalopia and visual field loss. One year later, she and her husband came in for genetic risk assessment. Testing revealed that he carried a USH2A mutation (c.15364T > C), leading the couple to a 50% risk of having a baby with Usher syndrome (pseudodominance).