Germline mutations predisposing to melanoma.

Nearly 15% of melanomas occur in patients with a family history and a subset of these patients have a germline mutation in a melanoma predisposing gene. CDKN2A mutations are responsible for the majority of hereditary melanoma, but many other susceptibility genes have been discovered in recent years, including CDK4, TERT, ACD, TERF2IP, POT1, MITF, MC1R, and BAP1. Additionally, melanoma risk is increased in mixed cancer syndromes caused by mutations in PTEN, BRCA2, BRCA1, RB1, and TP53. While early onset, multiple tumors, and family cancer history remain the most valuable clinical clues for hereditary melanoma, characteristic epithelioid cytology of melanocytic tumors may suggest an underlying BAP1 mutation. Herein, we review the clinical and histopathologic characteristics of melanocytic tumors associated with these germline mutations and discuss the role of genetic counseling.

De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing.

BACKGROUND: Wiedemann-Steiner Syndrome (WSS) is characterized by short stature, a variety of dysmorphic facial and skeletal features, characteristic hypertrichosis cubiti (excessive hair on the elbows), mild-to-moderate developmental delay and intellectual disability. [MIM#: 605130]. Here we report two unrelated children for whom clinical exome sequencing of parent-proband trios was performed at UCLA, resulting in a molecular diagnosis of WSS and atypical clinical presentation. CASE PRESENTATION: For patient 1, clinical features at 9 years of age included developmental delay, craniofacial abnormalities, and multiple minor anomalies. Patient 2 presented at 1 year of age with developmental delay, microphthalmia, partial 3-4 left hand syndactyly, and craniofacial abnormalities. A de novo missense c.4342T>C variant and a de novo splice site c.4086+G>A variant were identified in the KMT2A gene in patients 1 and 2, respectively. CONCLUSIONS: Based on the clinical and molecular findings, both patients appear to have novel presentations of WSS. As the hallmark hypertrichosis cubiti was not initially appreciated in either case, this syndrome was not suspected during the clinical evaluation. This report expands the phenotypic spectrum of the clinical phenotypes and KMT2A variants associated with WSS.

West Nile virus in mosquitoes of northern Ohio, 2003.

From June 19, 2003 to August 18, 2003, we surveyed the mosquitoes of Oberlin, OH, for West Nile Virus (WNV) infection using reverse transcriptase-polymerase chain reaction. A total of 12,055 mosquitoes, representing 17 species or species groups and 4 genera, were collected in gravid traps at seven sites throughout the city, with Culex pipiens/restuans being the most abundant and showing the highest minimum infection rate (MIR) of 0.78. This represents a decrease in WNV enzootic activity from the previous year. Both Cx. pipiens/restuans abundance and MIR increased significantly with date. However, we found no correlation between Cx. pipiens/restuans abundance and MIR.

Survey of Aedes triseriatus (Diptera: Culicidae) for Lacrosse encephalitis virus and West Nile virus in Lorain County, Ohio.

From June through September 2003, we conducted a survey of female Aedes triseriatus (Say) for infection with La Crosse encephalitis virus (family Bunyaviridae, genus Orthobunyavirus, LACV) and West Nile virus (family Flaviviridae, genus Flavivirus, WNV) at three locations in Lorain County, Ohio. To determine infection rate and seasonal variation of both viruses in the Ae. triseriatus population, Ae. triseriatus were collected weekly by using gravid traps and CO2-baited CDC light traps and tested for virus by using reverse transcriptase polymerase chain reaction. In total, 170 pools comprised of 2,143 females were tested for LACV, of which seven were positive; the maximum likelihood estimate of infection rate combined throughout the season was 3.22/1,000. None of 170 pools comprised of 2,158 females tested for WNV were positive. LACV-positive pools were detected between late July and early September.

West Nile virus in mosquitoes of Northern Ohio, 2001-2002.

From June 14 to August 30, 2001 and June 10 to August 22, 2002, the mosquitoes of Oberlin, Ohio were surveyed and tested for West Nile virus (WNV). Mosquitoes were trapped weekly using gravid traps and CO(2)-baited Centers for Disease Control light traps at seven sites in 2001 and eight sites in 2002 in woodlots within the city limits. A total of 12,151 mosquitoes, representing 14 species and one species group, were collected in gravid traps, with Culex pipiens/restuans being the most abundant, followed by Ochlerotatus triseriatus. In light traps, 12,510 mosquitoes were collected, with Aedes vexans being the most abundant, followed by Culex pipiens/restuans. All gravid trap collections were tested for WNV via reverse transcriptase-polymerase chain reaction. West Nile virus was first detected in July 2002. Of all species tested, the Cx. pipiens/restuans species group exhibited the highest minimum infection rate (MIR) and the greatest percentage of positive pools. Both the MIR and percent of positive pools increased significantly with the date, although abundance of Cx. pipiens/restuans in gravid trap collections did not.