Kallmann syndrome in a patient with Weiss-Kruszka syndrome and a de novo deletion in 9q31.2

Patients with deletions on chromosome 9q31.2 may exhibit delayed puberty, craniofacial phenotype including cleft lip/palate, and olfactory bulb hypoplasia. We report a patient with congenital HH with anosmia (Kallmann syndrome, KS) and a de novo 2.38 Mb heterozygous deletion in 9q31.2. The deletion breakpoints (determined with wholegenome linked-read sequencing) were in the FKTN gene (9:108,331,353) and in a non-coding area (9:110,707,332) (hg19). The deletion encompassed six protein-coding genes (FKTN, ZNF462, TAL2, TMEM38B, RAD23B, and KLF4). ZNF462 haploinsufficiency was consistent with the patient's Weiss-Kruszka syndrome (craniofacial phenotype, developmental delay, and sensorineural hearing loss), but did not explain his KS. In further analyses, he did not carry rare sequence variants in 32 known KS genes in whole-exome sequencing and displayed no aberrant splicing of 15 KS genes that were expressed in peripheral blood leukocyte transcriptome. The deletion was 1.8 Mb upstream of a KS candidate gene locus (PALM2AKAP2) but did not suppress its expression. In conclusion, this is the first report of a patient with Weiss-Kruszka syndrome and KS. We suggest that patients carrying a microdeletion in 9q31.2 should be evaluated for the presence of KS and KS-related features.Peer reviewe

Brachytherapy of Choroidal Melanomas Less Than 10 mm in Largest Basal Diameter Comparison of 10-mm and 15-mm Ruthenium Plaques

Purpose: To compare tumor control, vision, and complications between patients with a choroidal melanoma of Design: Retrospective, comparative case series. Participants: One hundred sixty-four consecutive patients with a choroidal melanoma of Methods: Diagnosis was based on growth or high-risk characteristics. The apical dose was 100 to 120 Gy aiming to deliver >= 250 Gy to the sclera. Plaque positioning was modeled retrospectively. An increase of >= 0.3 mm in thickness and >= 0.5 mm in LBD indicated local recurrence. Outcomes were compared with cumulative incidence analysis and Cox regression. Median follow-up time for patients still alive was 8.4 years. Main Outcome Measures: Recurrence rate, low vision, blindness, radiation maculopathy, and optic neuropathy. Results: Melanomas treated with the 10-mm plaque were smaller (median thickness, 1.9 mm vs. 2.6 mm; LBD, 7.1 mm vs. 8.6 mm) and located closer to foveola (median, 2.0 mm vs. 2.8 mm) than those treated with the 15-mm plaque (P <0.001). The 2 plaques provided a safety margin in 43% versus 40% eyes, provided no safety margin to guard foveola in 17% versus 33%, and did not entirely cover tumor mainly close to the disc in 32% versus 18% of eyes, respectively (P = 0.052). The incidence of a local recurrence was comparable (13% vs. 15% at 10 years; P = 0.31) and associated with plaque positioning (hazard ratio [HR], 2.81 for no safety margin; P = 0.041). At 5 years, the incidence of low vision was 14% versus 24%, and that of blindness was 3% versus 6%. Distance to the foveola was associated with loss of both levels of vision (HR, 0.65 per 1 mm vs. 0.68 per 1 mm; P Conclusions: The 10-mm ruthenium plaque contributes to better visual preservation, particularly with tumors close to fovea, without increase in local recurrence rate, and may therefore be preferable to the 15-mm plaque. (C) 2020 by the American Academy of OphthalmologyPeer reviewe

Sää- ja ilmastoriskien hallinta ja tietolähteet Suomessa

Raportissa kuvaillaan sää- ja ilmastoriskien hallintaa ja siihen liittyvien tietolähteiden käyttöä Suomessa. Raportti perustuu kolmeen erilliseen, mutta toisiaan tukevaan työvaiheeseen. Ensimmäinen työvaihe koostui kahdesta verkkokyselystä, joista toinen oli suunnattu kunnille ja toinen suomalaisille organisaatioille yleisesti. Kyselyillä kartoitettiin vastaajien kokemuksia sää- ja ilmastoriskeistä, niiden hallintaa ja käytettyjä tietolähteitä. Toisen työvaiheen muodosti sidosryhmätyöpaja, jonka tavoitteena oli vahvistaa kyselyn pääpiirteiset tulokset ja kerätä ajatuksia sää- ja ilmastoriskien hallinnan ja sitä tukevien palveluiden kehittämiseen. Kolmas työvaihe koostui kirjallisuusperustaisesta toimialakartoituksesta, jossa koottiin yhteen tietoa sää- ja ilmastoriskeistä ja niiden hallinnasta valituilla yhteiskunnan aloilla (vesivarat, vesihuolto, energia, maatalous, liikenne, matkailu, kuntasektori ja finanssiala). Kukin kolmesta työvaiheesta tuloksineen on esitelty raportissa erikseen. Tulokset viittaavat siihen, että vaikka säällä ja ilmastolla on merkittäviä vaikutuksia yhteiskunnan eri aloille ja toimijoille, on niiden aiheuttamien riskien hallinta vaihtelevaa. Yhteistyö eri muodoissaan koetaan tärkeäksi parannettaessa kykyä sää- ja ilmastoriskien hallintaan. Raportti perustuu ELASTINEN-hankkeessa tehtyyn työhön. Tämä julkaisu on toteutettu osana valtioneuvoston vuoden 2015 selvitys- ja tutkimussuunnitelman toimeenpanoa

Recombinant Human FSH Treatment Outcomes in Five Boys With Severe Congenital Hypogonadotropic Hypogonadism

Context Recombinant human FSH (r-hFSH), given to prepubertal boys with hypogonadotropic hypogonadism (HH), may induce Sertoli cell proliferation and thereby increase sperm-producing capacity later in life. Objective To evaluate the effects of r-hFSH, human chorionic gonadotropin (hCG), and testosterone (T) in such patients. Design and Setting Retrospective review in three tertiary centers in Finland between 2006 and 2016. Patients Five boys: ANOS1 mutation in two, homozygous PROKR2 mutation in one, FGFR1 mutation in one, and homozygous GNRHR mutation in one. Prepubertal testicular volume (TV) varied between 0.3 and 2.3 mL; three boys had micropenis, three had undergone orchidopexy. Interventions Two boys received r-hFSH (6 to 7 months) followed by r-hFSH plus hCG (33 to 34 months); one received T (6 months), then r-hFSH plus T (29 months) followed by hCG (25 months); two received T (3 months) followed by r-hFSH (7 months) or r-hFSH plus T (8 months). Main Outcome Measures TV, inhibin B, anti-Müllerian hormone, T, puberty, sperm count. Results r-hFSH doubled TV (from a mean ± SD of 0.9 ± 0.9 mL to 1.9 ± 1.7 mL; P < 0.05) and increased serum inhibin B (from 15 ± 5 ng/L to 85 ± 40 ng/L; P < 0.05). hCG further increased TV (from 2.1 ± 2.3 mL to 8.6 ± 1.7 mL). Two boys with initially extremely small testis size (0.3 mL) developed sperm (maximal sperm count range, 2.8 to 13.8 million/mL), which was cryopreserved. Conclusions Spermatogenesis can be induced with gonadotropins even in boys with HH who have extremely small testes, and despite low-dose T treatment given in early puberty. Induction of puberty with gonadotropins allows preservation of fertilityPeer reviewe

BAP1 Germline Mutations in Finnish Patients with Uveal Melanoma

Purpose: Germline mutations of the BRCA1-associated protein-1 gene (BAP1) predispose carriers to uveal melanoma. We report the population-based frequency of germline pathogenic variants of BAP1 in Finnish patients with uveal melanoma who live in a high-risk region for this cancer. Design: Cohort study. Participants: In Finland, uveal melanomas are treated centrally in the Ocular Oncology Service, Helsinki University Hospital. We collected clinical data and genomic DNA from 148 of 188 consecutive patients diagnosed from January 2010 through December 2012. Seven of these patients from 6 families had a history of uveal melanoma in 1 relative, and 2 patients from 2 additional families had such a history in 2 relatives. Methods: Sequencing BAP1. Main Outcome Measures: Pathogenic variants in BAP1. Results: We found 2 different pathogenic variants in BAP1 in 3 patients. Two patients had a single nucleotide insertion in exon 14 resulting in a shift of reading frame. Both had a family history of uveal melanoma in at least 1 relative. One patient without a family history of uveal melanoma had a single nucleotide substitution in the conserved splice donor site of intron 2. BAP1 cancer predisposition syndrome-related cancers were present in all 3 families. The overall frequency of BAP1 pathogenic variants was 2.0% (3/148; 95% confidence interval, 0.4-5.8), the frequency among patients 50 years of age or younger was 3.6% (1/28; 95% confidence interval, 0.1-18), and a pathogenic variant was detected in 2 of 8 families with a history of uveal melanoma. Conclusions: The frequency of BAP1 germline pathogenic variants in consecutive Finnish patients with uveal melanoma who come from a high-risk region for the development of this cancer is comparable with reports from other populations. (C) 2016 by the American Academy of Ophthalmology.Peer reviewe