Clinical spectrum of females with HCCS mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects (MLS) syndrome

Background: Segmental Xp22.2 monosomy or a heterozygous HCCS mutation is associated with the microphthalmia with linear skin defects (MLS) or MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome, an X-linked disorder with male lethality. HCCS encodes the holocytochrome c-type synthase involved in mitochondrial oxidative phosphorylation (OXPHOS) and programmed cell death. Methods: We characterized the X-chromosomal abnormality encompassing HCCS or an intragenic mutation in this gene in six new female patients with an MLS phenotype by cytogenetic analysis, fluorescence in situ hybridization, sequencing, and quantitative real-time PCR. The X chromosome inactivation (XCI) pattern was determined and clinical data of the patients were reviewed. Results: Two terminal Xp deletions of ≥11.2 Mb, two submicroscopic copy number losses, one of ~850 kb and one of ≥3 Mb, all covering HCCS, 1 nonsense, and one mosaic 2-bp deletion in HCCS are reported. All females had a completely (>98:2) or slightly skewed (82:18) XCI pattern. The most consistent clinical features were microphthalmia/anophthalmia and sclerocornea/corneal opacity in all patients and congenital linear skin defects in 4/6. Additional manifestations included various ocular anomalies, cardiac defects, brain imaging abnormalities, microcephaly, postnatal growth retardation, and facial dysmorphism. However, no obvious clinical sign was observed in three female carriers who were relatives of one patient. Conclusion: Our findings showed a wide phenotypic spectrum ranging from asymptomatic females with an HCCS mutation to patients with a neonatal lethal MLS form. Somatic mosaicism and the different ability of embryonic cells to cope with an OXPHOS defect and/or enhanced cell death upon HCCS deficiency likely underlie the great variability in phenotypes

Ein municipaler Quaestor von Celeia im mittleren Murtal: Die Grabinschrift vom Kirchberg bei Deutschfeistritz, Steiermark

 Rimski  nagrobni  napis  je  bil  odkrit  leta  2004  v  cerkvi  prikraju Deutschfeistritz v dolini Mure okoli 20 km severozahod-no od Gradca. Ohranjen je fragmentarno, delno je tudi poško-dovan zaradi sekundarne rabe kot gradbeni element. Eden izmeddružinskih  članov,  katerim  je  bil  nagrobnik  posvečen,  je  bilprej neznan municipalni kvestor iz Celeje. Na osnovi dimenzijmarmornega kosa lahko sklepamo, da je nekoč moral biti delmonumentalne  grobne  arhitekture.  Najdišče  groba  ni  znano,gotovo pa je pripadalo administrativnemu območju Flavije Solve.V tem arheološkem okolju so našli več ostankov iz rimske dobe:npr.  dva  miljnika  in  celoten  niz  ostankov  naselbine./A Roman tombstone inscription came to light in 2004 in achurch  near  Deutschfeistritz  in  the  Mur  valley  about  20  kmnorthwest  of  Graz.  It  had  been  fragmented  and  partly  dam-aged in the course of secondary use as a building element. Thebeginning of the text is not preserved. One of the family mem-bers  to  be  commemorated  was  a  previously  unknown  munic-ipal quaestor from Celeia. Due to its dimensions, the marblepiece once must have been part of a monumental tomb struc-ture.  The  site  of  the  tomb  is  unidentified  but  it  certainly  be-longed to the administrative area of Flavia Solva. The archae-ological  surroundings  contain  several  remains  from  the  Ro-man  period,  e.g.  two  milestones  and  a  whole  series  of  settle-ment  remains

The acrocentric part of der(Y)t(Y;acro)(q12;p1?2) contains D15Z1 sequences in the majority of cases

Chromosomal heteromorphisms (CHMs) are currently largely disregarded in human genetic diagnostics. One exception is der(Y)t(Y;acro)(q12;p1?2), which has at least been mentioned in karyotypes and discussed in reports. This derivative is frequently observed in healthy males with idiopathic infertility, which is not uncommon for CHMs. Here, we present the first systematic fluorescence in situ hybridization (FISH)-based study of 7 carriers of der(Y)t(Y;acro)(q12;p1?2). Specific probes for 15p11.2 (D15Z1) and 22p11.2 (D22Z4) were applied to answer the question of whether either of the short arms may be involved in the formation of the derivative Y-chromosome. In 6 out of 7 cases, specific staining was achieved using the D15Z1 probe, while the derivative acrocentric chromosomal region was not positive for D22Z4 in any of the 7 cases.In conclusion, this study implies that the acrocentric chromosomal region is derived from chromosome 15 in the majority of cases with der(Y)t(Y;acro)(q12;p1?2)