Hereditary transthyretin amyloidosis is a severe, adult-onset autosomal dominant inherited systemic disease predominantly affecting the peripheral and autonomic nervous system, heart, kidney, and the eyes. We present a case of a Caucasian 65-year-old man with cardiac amyloidosis and the homozygous mutation Val142Ile (classically, Val122Ile) in the transthyretin gene. We provide a genotype-phenotype correlation regarding the genetic status of both heterozygous and homozygous individuals and their clinical conditions at the time of genetic testing.

[This corrects the article DOI: 10.3389/fnins.2021.604715.].

Chorea-Acanthocytosis (ChAc), a rare autosomal recessive inherited neurological disorder, originated from variants in Vacuolar Protein Sorting 13 homolog A (VPS13A) gene. The main symptoms of ChAc contain hyperkinetic movements, seizures, cognitive impairment, neuropsychiatric symptoms, elevated serum biochemical indicators, and acanthocytes detection in peripheral blood smear. Recently, researchers found that epilepsy may be a presenting and prominent symptom of ChAc. Here, we enrolled a consanguineous family with epilepsy and non-coordinated movement. Whole exome sequencing was employed to explore the genetic lesion of the family. After data filtering, co-separation analysis was performed by Sanger sequencing and bioinformatics analysis, the homozygous nonsense variant (NM_033305.2: c.8282C>G, p.S2761X) of VPS13A were identified which could be genetic factor of the patient. No other meaningful mutations were detected. This mutation (p.S2761X) led to a truncated protein in exon 60 of the VPS13A gene, was simultaneously absent in our 200 local control participants. The homozygous mutation (NM_033305.2: c.8282C>G, p.S2761X) of VPS13A may be the first time be identified in ChAc patient with epilepsy. Our study assisted to the diagnosis of ChAc in this patient and contributed to the genetic diagnosis and counseling of families with ChAc presented as epilepsy. Moreover, we further indicated that epilepsy was a crucial phenotype in ChAc patients caused by VPS13A mutations.

Alteration of the KPTN gene, responsible for the coding of kaptin (a protein involved in actin cytoskeletal dynamics), causes a syndrome characterized by macrocephaly, neurodevelopmental delay and epileptic seizures. We report the first Brazilian case of KPTN gene variation, previously described in nine subjects from four interlinked families from an Amish community in Ohio, two Estonian siblings and a 9-year-old boy from Kansas City. We report a case of KPTN-related syndrome in a 5-year-old child which presented macrocephaly, muscular hypotonia, and global development delay. The neurological examination revealed below-expected performance in coordination and balance tests, dyspraxia, and hand-mouth synkinesia. Expressive language was characterized by phono-articulatory imprecision, abundance of phonological processes and morphosyntactic immaturity. Neuropsychological assessment revealed intellectual disability with impairment of verbal and executive functions. Exome sequencing was performed. Analysis revealed a homozygous 2-nucleotide duplication c.597_598dup p.(Ser200Ilefs*55) in the KPTN gene, which is predicted to lead to a translational frameshift and formation of a premature stop codon. The phenotypic profile is similar to the cases described in the other families. Presence of macrocephaly and delayed development indicate the possibility of KPTN gene variation. Genetic testing should be carried out at an early stage in order to reach a timely diagnosis.

Background: Limb-girdle muscular dystrophy (LGMD) is an increasingly heterogeneous category of inherited muscle diseases, mainly affecting the muscles of shoulder areas and the hip, segregating in both autosomal recessive and dominant manner. To-date, thirty-one loci have been identified for LGMD including seven autosomal dominant (LGMD type 1) and twenty four autosomal recessive (LGMD type 2) inherited loci. Methodology/Laboratory Examination: The present report describes a consanguineous family segregating LGMD2F in an autosomal recessive pattern. The affected individual is an 11-year-old boy having two brothers and a sister. Direct targeted next generation sequencing was performed for the single affected individual (VI-1) followed by Sanger sequencing. Results: Targeted next generation sequencing revealed a novel homozygous nonsense mutation (c.289C>T; p.Arg97∗) in the exon 3 of the delta-sarcoglycan (SGCD) gene, that introduces a premature stop codon (TCA), resulting in a nonsense mediated decay or a truncated protein product. Discussion and Conclusion: This is the first report of LGMD2F caused by an SGCD variant in a Pakistani population. The mutation identified in the present investigation extends the body of evidence implicating the gene SGCD in causing LGMD2F and might help in genetic counseling, which is more important to deliver the risk of carrier or affected in the future pregnancies.