Lack of evidence for association of UQCRC1 with autosomal dominant Parkinson's disease in Caucasian families
(Source: Neurogenetics)
Source: Neurogenetics - July 21, 2021 Category: Genetics & Stem Cells Source Type: research
Milestones in genetics of cerebellar ataxias
AbstractCerebellar ataxias (CAs) comprise a group of rare, neurological disorders characterized by extensive phenotypic and genetic heterogeneity. The core clinical feature is the cerebellar syndrome, which is often accompanied by other neurological or non-neurological signs. In the last 30 years, our understanding of the CA etiology has increased significantly, and numerous ataxia-associated genes have been discovered. Conventional variants or tandem repeat expansions, localized in the coding or non-coding DNA sequences, lead to hereditary ataxia, which can display different pattern s of inheritance. Advances in molecul...
Source: Neurogenetics - July 5, 2021 Category: Genetics & Stem Cells Source Type: research
ANK3 related neurodevelopmental disorders: expanding the spectrum of heterozygous loss-of-function variants
AbstractANK3 encodes multiple isoforms of ankyrin-G, resulting in variegated tissue expression and function, especially regarding its role in neuronal development. Based on the zygosity, location, and type,ANK3 variants result in different neurodevelopmental phenotypes. Autism spectrum disorder has been associated with heterozygous missense variants inANK3, whereas a more severe neurodevelopmental phenotype is caused by isoform-dependent, autosomal-dominant, or autosomal-recessive loss-of-function variants. Here, we present four individuals affected by a variable neurodevelopmental phenotype harboring a heterozygous frames...
Source: Neurogenetics - July 3, 2021 Category: Genetics & Stem Cells Source Type: research
Secondary biogenic amine deficiencies: genetic etiology, therapeutic interventions, and clinical effects
This study demonstrates the utility of genome-wide sequencing in further understanding the etiology and pathophysiology of neurometabolic conditions, and the potential of secondary neurotransmitter deficiencies to serve as novel therapeutic targets. As there was a largely favorable response to therapy in our case series, a careful trial of neurotransmitter replacement therapy should be considered in patients with cerebrospinal fluid (CSF) monoamines below reference range. (Source: Neurogenetics)
Source: Neurogenetics - July 2, 2021 Category: Genetics & Stem Cells Source Type: research
More evidence on TRIO missense mutations in the spectrin repeat domain causing severe developmental delay and recognizable facial dysmorphism with macrocephaly
AbstractTRIO is a Dbl family guanine nucleotide exchange factor (GEF) and an important regulator of neuronal development. Most truncating and missense variants affecting the Dbl homology domain ofTRIO are associated with a neurodevelopmental disorder with microcephaly (MIM617061). Recently, de novo missense variants affecting the spectrin repeat region of TRIO were associated with a novel phenotype comprising severe developmental delay and macrocephaly (MIM618825). Here, we provide more evidence on this newTRIO-associated phenotype by reporting two severely affected probands with de novo missense variants inTRIO affecting ...
Source: Neurogenetics - July 1, 2021 Category: Genetics & Stem Cells Source Type: research
Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases
AbstractParoxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age de...
Source: Neurogenetics - July 1, 2021 Category: Genetics & Stem Cells Source Type: research
Does genetic anticipation occur in familial Alexander disease?
We report a family with inherited AxD in which the mother presented with symptoms many years after her daughter. We reviewed the age of onset in all published cases of familial AxD and found that 32 of 34 instances of parent –offspring pairs demonstrated an earlier age of onset in offspring compared to the parent. We suggest that genetic anticipation occurs in familial AxD and speculate that genetic mosaicism could explain this phenomenon. (Source: Neurogenetics)
Source: Neurogenetics - July 1, 2021 Category: Genetics & Stem Cells Source Type: research
8p21.3 deletions are rare causes of non-syndromic autism spectrum disorder
AbstractAde novo 0.95 Mb 8p21.3 deletion had been identified in an individual with non-syndromic autism spectrum disorder (ASD) through high-resolution copy number variant analysis. Subsequent screening of in-house and publicly available databases resulted in the identification of six additional individuals with 8p21.3 deletions. Through case-based reasoning, we conclude that 8p21.3 deletions are rare causes of non-syndromic neurodevelopmental and neuropsychiatric disorders. Based on literature data, we highlight six genes within the region of minimal overlap as potential ASD genes or genes for neuropsychiatric disorders:D...
Source: Neurogenetics - July 1, 2021 Category: Genetics & Stem Cells Source Type: research
Pitt –Hopkins syndrome: phenotypic and genotypic description of four unrelated patients and structural analysis of corresponding missense mutations
AbstractPitt –Hopkins syndrome is an underdiagnosed neurodevelopmental disorder which is characterized by specific facial features, early-onset developmental delay, and moderate to severe intellectual disability. The genetic cause, a deficiency of the TCF4 gene, has been established; however, the underlying pa thological mechanisms of this disease are still unclear. Herein, we report four unrelated children with different de novo mutations (T606A, K607E, R578C, and V617I) located at highly conserved sites and with clinical phenotypes which present variable degrees of developmental delay and intellectual d isability. Thre...
Source: Neurogenetics - July 1, 2021 Category: Genetics & Stem Cells Source Type: research
Genotype –phenotype correlations of heterozygous HTRA1-related cerebral small vessel disease: case report and systematic review
This study aimed to describe these mutations to clarify factors playing a role in the clinical phenotype amongst these patients. We reported two unrelated families and performed a systematic review of all published cases of heterozygousHTRA1-related CSVD. The clinical phenotype severity was independently related to the pathogenicity score (CADD score;p < 0.05) and mutation in the loop 3/loop D domains (p = 0.05); the pathogenicity score was also associated with exon distribution. More importantly, patients with mutations in exon 4 (p = 0.0001) or vascular risk factors (p < 0.05) presented with more ...
Source: Neurogenetics - June 29, 2021 Category: Genetics & Stem Cells Source Type: research
