Hexanucleotide repeat expansions in the C9ORF72 gene have been shown to be responsible for both familial and sporadic frontotemporal dementia/amyotrophic lateral sclerosis.
Alpha-synuclein (α-syn) is a major component of Lewy bodies, which are the pathological hallmark in Parkinson's disease, and its genetic mutations cause familial forms of Parkinson's disease.
Inactivating variants of the aryl hydrocarbon receptor-interacting protein (AIP)-coding gene are the genetic cause of a subset of familial isolated pituitary adenomas (FIPA).
An expanded GGGGCC hexanucleotide of more than 30 repeats (termed (G4C2)<sub>30+</sub>) within C9orf72 is the most prominent mutation in familial frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS) (termed C9<sup>+</sup>).
In Denmark, the national HNPCC register has been granted an exception to send unsolicited letters with information on hereditary colorectal cancer and an invitation to genetic counseling to members of families with familial and hereditary colorectal cancer.
In the longitudinal Frontotemporal Dementia Risk Cohort, presymptomatic mutation carriers and non-carriers from families with familial frontotemporal dementia due to microtubule-associated protein tau (MAPT) and progranulin (GRN) mutations underwent a clinical assessment and multimodal MRI at baseline, 2-, and 4-year follow-up.
Subsequent studies have also insinuated mutations in leucine repeat kinase-2 (LRRK2), Parkin, PTEN-induced putative kinase 1 (PINK1), as well as DJ-1 causing familial forms of PD.
Human genetics studies have linked LRRK2 as a major genetic contributor to familial and sporadic Parkinson's disease (PD), a neurodegenerative movement disorder that inflicts millions worldwide.
<b>Background:</b> Pathogenic variants in ALS genes are known to be present in up to 70% of familial and 10% of apparently sporadic ALS cases, and can be associated with risks for ALS only, or risks for other neurodegenerative diseases (eg. frontotemporal dementia).
Genetic variability in LRRK2 has been unequivocally established as a major risk factor for familial and sporadic forms of PD in ethnically diverse populations.
<b>Background:</b> Pathogenic variants in ALS genes are known to be present in up to 70% of familial and 10% of apparently sporadic ALS cases, and can be associated with risks for ALS only, or risks for other neurodegenerative diseases (eg. frontotemporal dementia).
Mutations in the GRN gene coding for progranulin (PGRN) are responsible for many cases of familial frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein 43 (TDP-43)-positive inclusions (FTLD-TDP).
Mutations in the genes encoding for alpha-synuclein (aSyn), LRRK2, and tau have been associated with familial and sporadic forms of the disease. aSyn is the major component of Lewy bodies and Lewy neurites, which are pathognomonic protein inclusions in PD.
Rare truncating BRCA2K3326X (rs11571833) and pathogenic CHEK2 rs17879961" genes_norm="11200">I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases.
The MM-VCEP began optimizing ACMG/AMP rules for RUNX1 because many germline variants have been described in patients with familial platelet disorder with a predisposition to acute myeloid leukemia, characterized by thrombocytopenia, platelet functional/ultrastructural defects, and a predisposition to hematologic malignancies.
In Denmark, the national HNPCC register has been granted an exception to send unsolicited letters with information on hereditary colorectal cancer and an invitation to genetic counseling to members of families with familial and hereditary colorectal cancer.
Notably, mutations in the LIR-motif proteins p62 (SQSTM1) and optineurin (OPTN) contribute to familial forms of frontotemporal dementia and amyotrophic lateral sclerosis.