scholarly journals New Cav1.2 Channelopathy with High-Functioning Autism, Affective Disorder, Severe Dental Enamel Defects, a Short QT Interval, and a Novel CACNA1C Loss-of-Function Mutation

2020 ◽  
Vol 21 (22) ◽  
pp. 8611
Author(s):  
Dominique Endres ◽  
Niels Decher ◽  
Isabell Röhr ◽  
Kirsty Vowinkel ◽  
Katharina Domschke ◽  
...  
Keyword(s):  
Protein Function ◽  
High Functioning Autism ◽  
Dental Enamel ◽  
Autism Spectrum ◽  
Severe Form ◽  
Loss Of Function ◽  
Enamel Defects ◽  
High Functioning ◽  
Electrophysiological Studies ◽  
Genetically Determined

Complex neuropsychiatric-cardiac syndromes can be genetically determined. For the first time, the authors present a syndromal form of short QT syndrome in a 34-year-old German male patient with extracardiac features with predominant psychiatric manifestation, namely a severe form of secondary high-functioning autism spectrum disorder (ASD), along with affective and psychotic exacerbations, and severe dental enamel defects (with rapid wearing off his teeth) due to a heterozygous loss-of-function mutation in the CACNA1C gene (NM_000719.6: c.2399A > C; p.Lys800Thr). This mutation was found only once in control databases; the mutated lysine is located in the Cav1.2 calcium channel, is highly conserved during evolution, and is predicted to affect protein function by most pathogenicity prediction algorithms. L-type Cav1.2 calcium channels are widely expressed in the brain and heart. In the case presented, electrophysiological studies revealed a prominent reduction in the current amplitude without changes in the gating behavior of the Cav1.2 channel, most likely due to a trafficking defect. Due to the demonstrated loss of function, the p.Lys800Thr variant was finally classified as pathogenic (ACMG class 4 variant) and is likely to cause a newly described Cav1.2 channelopathy.

Social Communication and Structural Language of Girls With High-Functioning Autism Spectrum Disorder

2020 ◽  
Vol 51 (4) ◽  
pp. 1139-1155
Author(s):  
Jenny M. Burton ◽  
Nancy A. Creaghead ◽  
Noah Silbert ◽  
Allison Breit-Smith ◽  
Amie W. Duncan ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Adaptive Behavior ◽  
Social Communication ◽  
High Functioning Autism ◽  
Autism Spectrum ◽  
Vineland Adaptive Behavior Scales ◽  
High Functioning ◽  
Expressive Communication ◽  
Vineland Adaptive Behavior ◽  
Structural Language

Purpose The purpose of this study was to characterize social communication and structural language of school-age girls with high-functioning autism spectrum disorder (HF-ASD) compared to a matched group of girls who are typically developing (TD). Method Participants were 37 girls between 7;5 and 15;2 (years;months)—18 HF-ASD and 19 TD. Children completed the Test of Pragmatic Language–Second Edition (TOPL-2) and Clinical Evaluation of Language Fundamentals–Fifth Edition. Parents completed the Children's Communication Checklist–2 United States Edition (CCC-2) and Receptive and Expressive Communication subdomains of the Vineland Adaptive Behavior Scales–Second Edition. Results In the area of social communication, girls with HF-ASD earned significantly lower scores and were more often classified as having an impairment on the TOPL-2 and the CCC-2. However, 28% and 33% earned average scores on the TOPL-2 and the CCC-2, respectively. In the area of structural language, no significant differences were found between groups on Clinical Evaluation of Language Fundamentals–Fifth Edition indexes. In contrast, girls with HF-ASD earned significantly lower scores and were more often classified as having an impairment on the Vineland Adaptive Behavior Scales–Second Edition. Sixty-one percent and 83% scored below average on the Receptive and Expressive Communication subdomains, respectively. Conclusions It has been argued that girls with HF-ASD, when compared to boys with HF-ASD, may have advantages for social communication and structural language that mask their impairments. However, when compared to girls who are TD, girls with HF-ASD demonstrated impaired social communication and structural language. Clinicians should include and carefully examine multiple sources of information when assessing girls with HF-ASD.

scholarly journals Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype

2021 ◽  
Author(s):  
Meena Balasubramanian ◽  
Alexander J. M. Dingemans ◽  
Shadi Albaba ◽  
Ruth Richardson ◽  
Thabo M. Yates ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Protein Function ◽  
Autism Spectrum ◽  
Loss Of Function ◽  
Mild Intellectual Disability ◽  
Related Disorder ◽  
Feeding Difficulties ◽  
Facial Phenotype ◽  
Novel Variants ◽  
Common Behaviour

AbstractWitteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10–12.

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