Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

LEAD-ANTIMONY SULFOSALTS FROM TUSCANY. IX MARRUCCIITE, Hg3Pb16Sb18S46, A NEW SULFOSALT FROM BUCA DELLA VENA MINE. APUAN ALPS: DEFINITION AND CRYSTAL STRUCTURE

Marrucciite, Hg3Pb16Sb18S46, is a new sulfosalt discovered in the Fe-Ba deposit of Buca della Vena, Apuan Alps (Italy). It occurs as black acicular metallic crystals in calcite veins; reflectance values in air are (R %; λ nm): 33.1 (470), 30.0 (546), 28.8 (589), 26.5 (650). Marrucciite is monoclinic, space group C2/m, with a 48.32(1) Å, b 4.117(1) Å, c 24.056(5) Å, β 118.84(3)°, V 4192(3) Å3, Z = 2, Dcalc. = 6.00 g/cm3; a 2b superstructure is present. Main lines of the X-ray diffraction powder pattern [d (in Å), I (main hkl)]: 4.02, 33 (12.0.3, 802); 3.480, 64 (803, 604); 3.418, 88 (607, 10.0.2, 314) ; 3.106, 31 (9.1.4); 2.994, 100 (11.1.2); 2.922, 41 (11.1.1); 2.056, 52 (020); 1.764, 41 (627). Electron microprobe analysis gave (wt.%; mean of 4 spot analyses): Cu 0.18(12), Hg 7.90(9), Pb 42.41(7), Sb 29.71(7), S 19.47(18), Cl 0.06(2), sum 99.73(14). The chemical formula (basis: 46 (S + Cl) at.) is Cu0.21Hg2.98Pb15.46Sb18.44S45.87Cl0.13, giving the stoichiometric one Hg3Pb16Sb18S46 that fulfils the charge balance. X-ray single crystal study (R = 9.56 %) revealed a complex structure, with Hg in two specific distorted octahedral coordinations (2 short distances each, close to 2.36 Å A). There are 40 other independent positions: 7 Pb, 2 (Pb, Sb), 8 Sb and 23 S. The general architecture of the structure is strongly related to that of hexagonal Ba12Bi24S48, with three types of Me10S14 rods (× 2) around a HgSb2Pb4S4 central column. It explains the pseudo-hexagonal symmetry (a/2 ∼ c; β ∼ 120°). A strong topologic relationship exists also between marrucciite and scainiite. Like rouxelite, the other coexisting Hg bearing sulfosalt, marrucciite was formed by hydrothermal process during the Apenninic tectono-metamorphic event