ABSTRACT
Spastic paraplegia type 7 (SPG7) is one of the most common forms of autosomal recessive hereditary spastic paraplegia, which can lead to a hybrid spastic-ataxic phenotype. Recently, novel complicated forms of SPG7, including cognitive and social impairment phenotypes, have been reported. We present a SPG7 case with two pathogenic variants in compound heterozygosity in the SPG7 gene, featuring a cerebellar cognitive affective syndrome with psychosis not yet described in the literature.
Subject(s)
Cognitive Dysfunction , Psychotic Disorders , ATPases Associated with Diverse Cellular Activities/genetics , Cognitive Dysfunction/genetics , Humans , Metalloendopeptidases/genetics , Mutation , Phenotype , Psychotic Disorders/complications , Psychotic Disorders/geneticsABSTRACT
Subacute symmetrical proximal muscle weakness and persistent elevated creatine kinase levels are typical of immune-mediated necrotising myopathy (IMNM). These conditions are accompanied by copious myofibre necrosis, degeneration and regeneration with minimal to no inflammation on muscle biopsy. We report two cases (case 1 and case 2) of asymptomatic IMNM from different families with hyperCKaemia associated with positive anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, respectively, and we also reviewed the literature. There are only a few previous descriptions of patients with asymptomatic IMNM.The disease onset could be insidious and lead to delayed diagnosis and treatment. We recommend testing for the anti-HMGCR and anti-SRP antibodies in patients with idiopathic hyperCKaemia because they could show no symptoms of this disorder.
Subject(s)
Autoantibodies/blood , Creatine Kinase/blood , Hydroxymethylglutaryl CoA Reductases/immunology , Immunoglobulins, Intravenous/administration & dosage , Myositis , Signal Recognition Particle/immunology , Asymptomatic Diseases , Biopsy/methods , Female , Humans , Immunologic Factors/administration & dosage , Male , Middle Aged , Muscle Weakness/diagnosis , Muscle Weakness/etiology , Muscle, Skeletal/pathology , Myositis/diagnosis , Myositis/immunology , Myositis/physiopathology , Necrosis/pathology , Treatment OutcomeABSTRACT
BACKGROUND: Xeroderma pigmentosum (XP) is a rare, genetically heterogeneous, autosomal recessive disorder caused by defects in the genes involved in repairing DNA damaged by ultraviolet radiation. These defects lead to a propensity to develop skin cancer at early ages as a hallmark, and progressive neurological degeneration can be observed in around 25% of patients. Eight clinically heterogeneous groups have been identified so far (XPA to XPG and XPV). Xeroderma pigmentosum variant type (XPV) is associated with pathogenic variants in POLH on chromosome 6, and no neurological dysfunction has been seen in these cases. However, on the same chromosome, it has been shown that TREM2 is associated with some types of dementia, particularly in patients with a behavioral variant frontotemporal phenotype. METHODS: Gene mutational analysis was performed by whole-exome sequencing. RESULTS: We report a case of a Caucasian woman with XP that developed behavioral and cognitive impairment at age 37. Whole-exome sequencing identified novel homozygous variants in POLH c.638C>G (p.Ser213*) and TREM2 c.154C>T (p.Arg52Cys), classifying the patient as XPV and suggesting that her frontotemporal dementia phenotype could be related to the variant in TREM2. CONCLUSION: This paper describes a rare case of a patient with two novel variants in the same chromosome associated with XPV and early-onset dementia.
