Embryonic expression of the human MID1 gene and its mutations in Opitz syndrome

Opitz syndrome (G/BBB syndrome, MIM145410, and MIM300000) is a midline congenital malformation characterised by hypertelorism, hypospadias and oesophagolaryngotracheal defects leading to swallowing difficulties and hoarse voice. This condition is genetically heterogeneous with an X-linked recessive form mapped to Xp22.3 and at least one autosomal dominant form mapped to chromosome 22q11.2. Recently, mutations in MID1 have been identified in the X-linked form of the disease but the gene for the autosomal dominant form on 22q11 remains unknown. Here we report on MID1 mutations screening in a series of 14 patients with Opitz syndrome and the MID1 expression pattern in human embryos using hybridisation in situ. Finally, we investigated the contribution of chromosome X-inactivation studies to identify the X-linked form of the disease. Six MID1 mutations were identified in our series. All mutations were novel except the R495X mutation previously reported in three unrelated patients. We report heart and hindbrain expression of MID1 during early human development. Obligate carrier mothers showed a random pattern of X-inactivation. Vermis hypoplasia or agenesis was frequently present (4/9) in patients with MID1 mutation. The heart and hindbrain expression of MID1 during early human development further supports the view that heart defects and vermis hypoplasia or agenesis are features to be included in the malformative spectrum of the syndrome. Finally, the study of X-inactivation pattern in women does not help discrimination between X-linked and autosomal forms of the disease

BBS10 mutations are common in 'Meckel'-type cystic kidneys

International audienceBackground : Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, multisystemic disorder characterized by progressive retinal dystrophy, obesity, hypogenitalism, learning difficulties, renal abnormalities and postaxial polydactyly, with only the last two antenatally observable. BBS is inherited as an autosomal recessive disorder and 14 genes have been identified to date (BBS1-BBS14). In addition, a complex digenic inheritance has been established in some families. Mutations of the BBS10 gene on chromosome 12q21.2 account for 20% of BBS cases. Methods: Given the fact that mutations in BBS genes have already been found in Meckel-like fetuses, and in light of the major contribution of BBS10 to BBS, we sequenced the BBS10 gene in 20 fetal cases and a child diagnosed antenatally presenting characteristic renal anomalies and polydactyly, but without biliary dysgenesis. Results: We identified recessive mutations at the BBS10 locus in 5 cases, 4 fetuses and a child. Interestingly, one of them had situs ambiguus, a rare feature in BBS. In the child, BBS genes screening identified a heterozygous BBS6 nonsense mutation in addition to the homozygous BBS10 mutation, in accordance with the suggested multigenic inheritance of the disease. Conclusions: These results confirm that BBS is underdiagnosed antenatally, and should systematically be suspected in fetuses with severe cystic kidneys leading to oligoamnios and fetal or perinatal death. Moreover, this study confirms the high frequency of BBS10 mutations and particularly of the p.Cys91Leufs*5 allele, including in severe lethal cases

Familial CHARGE syndrome because of CHD7 mutation: Clinical intra- and interfamilial variability

SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

‘The Insignia of Women’: Dress, Gender and identity on the Roman funerary monument of Regina from Arbeia

The current study focuses on the Roman gravestone of a British woman named Regina who died in the second half of the second century at the Roman fort of Arbeia (South Shields) at the mouth of the Tyne and was commemorated by her Palmyrene husband. The paper examines the Latin and Aramaic inscriptions on Regina's gravestone, the depiction of her ethnic clothing and bodily adornment, and the portrayal of the deceased as a woman skilled in wool-working, in order to contextualize and understand the important messages the monument conveys about physical mobility, ethnicity, social standing and gender relationships on Rome's northern frontier