Fetal liver iron overload: The role of MR imaging

Objective: To assess the potential role of MR imaging in the diagnosis of fetal liver iron overload. Methods: We reviewed seven cases of abnormal liver signal in fetuses referred to MR imaging in a context of suspected congenital infection (n∈=∈2), digestive tract anomalies (n∈=∈3) and hydrops fetalis (n∈=∈2). The average GA of the fetuses was 31 weeks. The antenatal diagnoses were compared with histological data (n∈=∈6) and postnatal work-up (n∈=∈1). Results: Magnetic resonance imaging demonstrated unexpected abnormal fetal liver signal suggestive of iron overload in all cases. The iron overload was confirmed on postnatal biopsy (n∈=∈2) and fetopathology (n∈=∈4). The final diagnosis was hepatic hemosiderosis (haemolytic anaemia (n∈=∈2) and syndromal anomalies (n∈=∈2)) and congenital haemochromatosis (n∈=∈3). In all cases, the liver appeared normal on US. Conclusions: Magnetic resonance is the only imaging technique able to demonstrate liver iron overload in utero. Yet, the study outlines the fundamental role of MR imaging in cases of congenital haemochromatosis. The antenatal diagnosis of such a condition may prompt ante-(in the case of recurrence) or neonatal treatment, which might improve the prognosis. © 2010 European Society of Radiology.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm

International audienceIntracranial aneurysms (IAs) are acquired cerebrovascular abnormalities characterized by localized dilation and wall thinning in intracranial arteries, possibly leading to subarachnoid hemorrhage and severe outcome in case of rupture. Here, we identified one rare nonsense variant (c.1378A>T) in the last exon of ANGPTL6 (Angiopoietin-Like 6)—which encodes a circulating pro-angiogenic factor mainly secreted from the liver—shared by the four tested affected members of a large pedigree with multiple IA-affected case subjects. We showed a 50% reduction of ANGPTL6 serum concentration in individuals heterozygous for the c.1378A>T allele (p.Lys460Ter) compared to relatives homozygous for the normal allele, probably due to the non-secretion of the truncated protein produced by the c.1378A>T transcripts. Sequencing ANGPTL6 in a series of 94 additional index case subjects with familial IA identified three other rare coding variants in five case subjects. Overall, we detected a significant enrichment (p = 0.023) in rare coding variants within this gene among the 95 index case subjects with familial IA, compared to a reference population of 404 individuals with French ancestry. Among the 6 recruited families, 12 out of 13 (92%) individuals carrying IA also carry such variants in ANGPTL6, versus 15 out of 41 (37%) unaffected ones. We observed a higher rate of individuals with a history of high blood pressure among affected versus healthy individuals carrying ANGPTL6 variants, suggesting that ANGPTL6 could trigger cerebrovascular lesions when combined with other risk factors such as hypertension. Altogether, our results indicate that rare coding variants in ANGPTL6 are causally related to familial forms of IA