Myotonic dystrophy type 1 testing, 2024 revision: A technical standard of the American College of Medical Genetics and Genomics (ACMG).

Myotonic dystrophy type 1 (DM1) is a form of muscular dystrophy causing progressive muscle loss and weakness. Although clinical features can manifest at any age, it is the most common form of muscular dystrophy with onset in adulthood. DM1 is an autosomal dominant condition, resulting from an unstable CTG expansion in the 3'-untranslated region of the myotonic dystrophy protein kinase (DMPK) gene.

Patient Decisions to Receive Secondary Pharmacogenomic Findings and Development of a Multidisciplinary Practice Model to Integrate Results Into Patient Care.

Whole exome sequencing (WES) has the potential of identifying secondary findings that are predictive of poor pharmacotherapy outcomes. The purpose of this study was to investigate patients' wishes regarding the reporting of secondary pharmacogenomic findings. WES results (n = 106 patients) were retrospectively reviewed to determine the number of patients electing to receive secondary pharmacogenomic results.

Assessment of clinical workload for general and specialty genetic counsellors at an academic medical center: a tool for evaluating genetic counselling practices.

With genomics influencing clinical decisions, genetics professionals are exponentially called upon as part of multidisciplinary care. Increasing demand for genetic counselling, a limited workforce, necessitates practices improve efficiency. We hypothesised that distinct differences in clinical workload exist between various disciplines of genetic counselling, complicating practice standardisation and patient volume expectations.

Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy.

Objective: The early infantile epileptic encephalopathy type 13 (EIEE13, OMIM #614558) results from de novo missense mutations of SCN8A encoding the voltage-gated sodium channel Nav1.6. More than 20% of patients have recurrent mutations in residues Arg1617 or Arg1872.

Mutations in the human UBR1 gene and the associated phenotypic spectrum.

Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n = 29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families.

Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features.

SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system. Despite its important developmental roles, SOX5 disruption has yet to be associated with human disease. We report one individual with a reciprocal translocation breakpoint within SOX5, eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent), and seven individuals with larger 12p12 deletions encompassing SOX5.

Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations.

A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here.

Johanson-Blizzard syndrome with mild phenotypic features confirmed by UBR1 gene testing.

Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive condition associated with exocrine pancreatic insufficiency, and is characterized by hypoplastic nasal alae, mental retardation, sensorineural hearing loss, short stature, scalp defects, dental abnormalities and abnormal hair patterns. Growth hormone deficiency, hypopituitarism, and impaired glucagon secretion response to insulin-induced hypoglycemia have been reported. Congenital heart defects have also been described in this condition.

Germline mutations in PTEN and SDHC in a woman with epithelial thyroid cancer and carotid paraganglioma.

Background: A 43-year-old woman presented to a cancer genetics clinic for a genetic risk assessment because of her personal history of multiple neoplasias. At 37 years of age, she was diagnosed with multifocal papillary thyroid cancer, and within a year was further diagnosed with a paraganglioma of the left common carotid artery. Two years later, she was diagnosed with a paraganglioma of the right carotid body.