ABSTRACT
PURPOSE: Neurodevelopmental disorders (NDDs) encompass a spectrum of genetically heterogeneous disorders with features that commonly include developmental delay, intellectual disability, and autism spectrum disorders. We sought to delineate the molecular and phenotypic spectrum of a novel neurodevelopmental disorder caused by variants in the GNAI1 gene. METHODS: Through large cohort trio-based exome sequencing and international data-sharing, we identified 24 unrelated individuals with NDD phenotypes and a variant in GNAI1, which encodes the inhibitory Gαi1 subunit of heterotrimeric G-proteins. We collected detailed genotype and phenotype information for each affected individual. RESULTS: We identified 16 unique variants in GNAI1 in 24 affected individuals; 23 occurred de novo and 1 was inherited from a mosaic parent. Most affected individuals have a severe neurodevelopmental disorder. Core features include global developmental delay, intellectual disability, hypotonia, and epilepsy. CONCLUSION: This collaboration establishes GNAI1 variants as a cause of NDDs. GNAI1-related NDD is most often characterized by severe to profound delays, hypotonia, epilepsy that ranges from self-limiting to intractable, behavior problems, and variable mild dysmorphic features.
Subject(s)
Intellectual Disability , Neurodevelopmental Disorders , Child , Developmental Disabilities/genetics , Humans , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Muscle Hypotonia/diagnosis , Muscle Hypotonia/genetics , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/genetics , Seizures/genetics , Exome SequencingABSTRACT
Encouraging family communication is an integral component of genetic counseling; therefore, we sought to identify factors impacting communication to family members at risk for Hypertrophic Cardiomyopathy (HCM). Participants (N = 383) completed an online survey assessing: 1) demographics (gender, genetic test results, HCM family history, and disease severity); 2) illness representations; 3) family functioning and cohesiveness; 4) coping styles; 5) comprehension of HCM autosomal dominant inheritance; and 6) communication of HCM risk information to at-risk relatives. Participants were a national sample of individuals with HCM, recruited through the Hypertrophic Cardiomyopathy Association. Data from 183 participants were analyzed using a logistic regression analysis, with family communication as a dichotomous dependent variable. We found that female gender and higher comprehension of autosomal dominant inheritance were significant predictors of participants' communication of HCM risk information to all their siblings and children. Our results suggest that utilizing interventions that promote patient comprehension (e.g., a teaching-focused model of genetic counseling) are important and may positively impact family communication within families with HCM.
Subject(s)
Cardiomyopathy, Hypertrophic/epidemiology , Family/psychology , Genetic Counseling/psychology , Interpersonal Relations , Adolescent , Adult , Communication , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
Emerging adulthood is an important period in the development of one's identity and autonomy. The ways in which identity and autonomy are viewed by emerging adults and how they impact quality of life (QoL) in individuals with early-onset neuromuscular conditions is not yet known. This study focused on understanding and exploring relationships between self-perceptions of emerging adulthood, autonomy, and QoL. Five previously validated measures were incorporated into an online survey and distributed to young adults with early-onset neuromuscular conditions and unaffected controls. Topics explored included individuals' views regarding their overall QoL, disease-specific QoL, components of emerging adulthood, and autonomy. We found that a sense of higher disease impact was associated with a lower Overall General QoL. Additionally, perceptions of key autonomy factors "negativity" and "instability" were uniquely associated with Overall General QoL in the case group as compared to controls, whereas "attitudinal autonomy" (attaining the ability to plan and follow through with goals) was important to this age group regardless of health status. The specific factors of emerging adulthood and autonomy that were significantly correlated with Overall General QoL can be used for developing targeted counseling and interventions to improve QoL for individuals and their families.
