Nature Genetics recently published damaging monoallelic SYK variants in six patients with immune dysregulation and systemic inflammation. These mutations were associated with immune deficiency, multi-organ inflammatory disease such as colitis, arthritis and dermatitis, and diffuse large B cell lymphomas.
A study published in Journal of Medical Genetics presented a novel severe skeletal dysplasia in a consaguineous Pakistani family. WGS data analyses identified a homozygous variant in GNPNAT1 encoding one of the enzymes required for syntheis of uridine diphosphate N-acetylglucosamine, which participates in protein glycosylation.
A recent study published in Human Mutation identified four independant probands with heterozygous, loss‐of‐function variants in POU4F1. All four probands identified in this study exhibited ataxia, intention tremor, and hypotonia.
Authors of a study published in Human Mutation identified three patients from two families with a lethal human multiple congenital anomaly syndrome encompassing diaphragmatic, pulmonary, and cardiovascular defects. These individuals presented compound heterozygous missense variants in ALDH1A2. ALDH1A2 is involved in the conversion of retinol (vitamin A) into retinoic acid (RA), which is an essential regulator of diaphragm and cardiovascular formation during embryogenesis.
A study recently published in The American Journal of Human Genetics identified eight unrelated indivuals with de novo mutations in DDB1. The affected individuals have a consistent phenotype of hypotonia, mild to moderate intellectual disability, and similar facies, including horizontal or slightly bowed eyebrows, deep-set eyes, full cheeks, a short nose, and large, fleshy and forward-facing earlobes, demonstrated in the composite face generated from the cohort. Digital anomalies, including brachydactyly and syndactyly, were common. Three older individuals have obesity.
Genetics in Medicine recently published a new developmental disorder caused by homozygous truncating variants in MAPKAPK5 in three patients of two unrelated families. This disorder is characterized by severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with an additional hypoplastic digit between the fourth and fifth digits of hands and/or feet.