Aarskog-Scott syndrome: a clinical study based on a large series of 111 male patients with a pathogenic variant in and management recommendations.

Background: Aarskog-Scott syndrome (AAS) is a rare condition with multiple congenital anomalies, caused by hemizygote variants in the gene. Its description was based mostly on old case reports, in whom a molecular diagnosis was not always available, or on small series. The aim of this study was to better delineate the phenotype and the natural history of AAS and to provide clues for the diagnosis and the management of the patients.

Mini-Exome Coupled to Read-Depth Based Copy Number Variation Analysis in Patients with Inherited Ataxias.

Next-generation sequencing (NGS) has an established diagnostic value for inherited ataxia. However, the need of a rigorous process of analysis and validation remains challenging. Moreover, copy number variations (CNV) or dynamic expansions of repeated sequence are classically considered not adequately detected by exome sequencing technique.

Marfan Sartan: a randomized, double-blind, placebo-controlled trial.

Aims: To evaluate the benefit of adding Losartan to baseline therapy in patients with Marfan syndrome (MFS).

Methods And Results: A double-blind, randomized, multi-centre, placebo-controlled, add on trial comparing Losartan (50 mg when <50 kg, 100 mg otherwise) vs. placebo in patients with MFS according to Ghent criteria, age >10 years old, and receiving standard therapy.

CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders.

Background: The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutation p.Arg117His in patients with congenital bilateral absence of the vas deferens (CBAVD) and in newborns screened for CF has created a dilemma.

Methods: Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.

Ultrastructural scoring of skin biopsies for diagnosis of vascular Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos syndrome (vEDS) results from a mutation in the gene encoding alpha-1, type III pro-collagen (COL3A1) and confers fragility to skin, ligament and vascular tissue. We tested the value of skin biopsy for diagnosis of vEDS through an ultrastructure scoring procedure. Study design was a multicentric, case-control, blinded trial consisting of two phases: phase 1 was to identify an ultra-structure score providing the best discriminative value for vEDS and phase 2 was to replicate this result in a different population.

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis.

Background: Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling.

Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma.

Background: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder predisposing humans to cutaneous and uterine leiomyomas; in 20% of affected families, type 2 papillary renal cell cancers (PRCCII) also occur with aggressive course and poor prognosis. HLRCC results from heterozygous germline mutations in the tumour suppressor fumarate hydratase (FH) gene.

Methods: As part of the French National Cancer Institute (INCa) 'Inherited predispositions to kidney cancer' network, sequence analysis and a functional study of FH were preformed in 56 families with clinically proven or suspected HLRCC and in 23 patients with isolated PRCCII (5 familial and 18 sporadic).

Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial.

Background: Vascular Ehlers-Danlos syndrome is a rare severe disease that causes arterial dissections and ruptures that can lead to early death. No preventive treatment has yet been validated. Our aim was to assess the ability of celiprolol, a β(1)-adrenoceptor antagonist with a β(2)-adrenoceptor agonist action, to prevent arterial dissections and ruptures in vascular Ehlers-Danlos syndrome.

Rationale and design of a randomized clinical trial (Marfan Sartan) of angiotensin II receptor blocker therapy versus placebo in individuals with Marfan syndrome.

Background: Recent studies have demonstrated that blockade of the angiotensin II type 1 receptor with losartan decreases aortic damage in an animal model of Marfan syndrome (a KI mouse model with a pathogenic mutation in the gene coding for fibrillin-1).

Aims: To demonstrate a beneficial effect of losartan on aortic dilatation when added to optimal therapy in patients with Marfan syndrome.

Methods: This is a multicentre, randomized, placebo-controlled, double-blind, clinical trial with a 2-year inclusion period and a 3-year follow-up period.

Missense mutations of conserved glycine residues in fibrillin-1 highlight a potential subtype of cb-EGF-like domains.

In six index cases/families referred for Marfan syndrome (MFS) molecular diagnosis, we identified six novel mutations in the FBN1 gene: c.1753G>C (p.Gly585Arg), c.

Three-dimensional analysis of the vertebral rotation associated with the lateral deviation in Marfan syndrome spinal deformity.

Unlabelled: Marfan syndrome (MFS) is a genetic disease often marked with the presence of scoliosis, which is poorly described in the literature. No three-dimensional analysis of the deformity in the literature is observed. Thirty patients diagnosed with MFS were prospectively included in our series.

Sagittal balance in scoliosis associated with Marfan syndrome: a stereoradiographic three-dimensional analysis.

Purpose: Marfan syndrome (MFS) is a genetic disease often marked by the presence of scoliosis. There is no three-dimensional analysis of the deformity in the literature. Our aim was to determine what kind of sagittal balance defines scoliosis associated with MFS, namely a flexion deformity, as it is in scoliosis associated with Chiari I or an extension deformity, as in adolescent idiopathic scoliosis (AIS).

Scoliotic curve patterns in patients with Marfan syndrome.

Purpose: Cases of "non-idiopathic" scoliosis are deemed atypical. These require a comprehensive work-up in order to choose the best treatment (and to determine an extent of fusion if needed). Marfan syndrome (MFS) is a genetic disease often marked with the presence of scoliosis, which is poorly described in the literature.

Recurrent rearrangements in the proximal 15q11-q14 region: a new breakpoint cluster specific to unbalanced translocations.

Unbalanced translocations, that involve the proximal chromosome 15 long arm and the telomeric region of a partner chromosome, result in a karyotype of 45 chromosomes with monosomy of the proximal 15q imprinted region. Here, we present our analysis of eight such unbalanced translocations that, depending on the parental origin of the rearranged chromosome, were associated with either Prader-Willi or Angelman syndrome. First, using FISH with specific BAC clones, we characterized the chromosome 15 breakpoint of each translocation and demonstrate that four of them are clustered in a small 460 kb interval located in the proximal 15q14 band.