Molecular analysis, pathogenic mechanisms, and readthrough therapy on a large cohort of Kabuki syndrome patients.

Kabuki syndrome (KS) is a multiple congenital anomalies syndrome characterized by characteristic facial features and varying degrees of mental retardation, caused by mutations in KMT2D/MLL2 and KDM6A/UTX genes. In this study, we performed a mutational screening on 303 Kabuki patients by direct sequencing, MLPA, and quantitative PCR identifying 133 KMT2D, 62 never described before, and four KDM6A mutations, three of them are novel. We found that a number of KMT2D truncating mutations result in mRNA degradation through the nonsense-mediated mRNA decay, contributing to protein haploinsufficiency.

Auxological and metabolic study in small for gestational age children during 2 years follow-up.

Objective: To compare auxological and metabolic status of preterm (PT) and fullterm (FT) small for gestational age (SGA) babies from birth until age 2 years and to study the role of intrauterine growth retardation (IUGR) in auxological and metabolic outcome in SGA babies.

Methods: We enrolled 44 SGA babies (22 FTs, 22 PTs) followed up six monthly. Anthropometric and metabolic measurements (fasting glucose, basal insulin level, total-cholesterol, triglycerides) were performed.

Influence of age, gender, and glucose tolerance on fasting and fed acylated ghrelin in Prader Willi syndrome.

Background & Aims: Prader Willi syndrome (PWS) is a genetic syndrome characterized by hyperphagia, morbid obesity, relative hypoinsulinemia and normal insulin sensitivity. PWS presents higher total (TG) and acylated ghrelin (AG) levels. The cause of this increase as well as the modulation of ghrelin secretion in fasting and feeding in relation to other metabolic parameters and glucose tolerance in PWS is largely unknown.

Effect of environment on growth: auxological and hormonal parameters in African and Italian children.

Objective: Genetic factors are the most important determinant of final height in developed countries, while in underprivileged countries food intake is crucial. Nutrients, in turn, may importantly affect IGF-IGFBP system which is a critical regulator of growth. The aim of this study was to evaluate the influence of nutrition on IGF system components, as well as on growth by comparing these variables in two selected populations of children living either in poor or in privileged environmental conditions.

The Italian National Survey for Prader-Willi syndrome: an epidemiologic study.

Twenty-five medical centers and the Prader-Willi Syndrome (PWS) Association collaborated on a study which attempted to identify all people with genetically confirmed diagnosis of PWS living in Italy. Investigators of the participating centers contacted PWS subjects and/or their family, filled in a specially developed form with the required data and forwarded this information by email. The study identified 425 subjects (209 males and 216 females, between the ages of 0.

Identification and molecular modelling of a novel familial mutation in the SRY gene implicated in the pure gonadal dysgenesis.

SRY gene is responsible for initiating male sexual differentiation. The protein encoded by SRY contains a homeobox (HMG) domain, which is a DNA-binding domain. Mutations of the SRY gene are reported to be associated with XY pure gonadal dysgenesis.

Endocrine and growth features in childhood craniopharyngioma: a mono-institutional study.

Objective: To evaluate growth and endocrine features in children with craniopharyngioma who were treated and followed up by a single institution between 1976 and 2004.

Patients: The records of 32 children, 18 males and 14 females, were evaluated. The mean follow-up period was 6.

Differences in size at birth are determined by differences in growth velocity during early prenatal life.

Physiologic interindividual differences in neonatal size are traditionally thought of as determined by differences in fetal growth occurring only in the second half of pregnancy. Whether possible differences in early intrauterine growth velocity are the effect of random growth fluctuations or may affect size at birth is still debated. This article aims at evaluating to what extent differences in neonatal size are accounted for by differences in fetal growth velocity.

Parental origin of Gsalpha mutations in the McCune-Albright syndrome and in isolated endocrine tumors.

Activating mutations of the Gsalpha gene are detected in different endocrine tumors, such as GH-secreting adenomas and toxic thyroid adenomas, and in hyperfunctioning glands from patients with McCune-Albright syndrome (MAS). There is increasing evidence that the Gsalpha gene is subjected to imprinting control and that Gsalpha imprinting plays a key role in the pathogenesis of different human diseases. The aim of this study was to investigate the presence of a parent specificity of Gsalpha mutations in 10 patients affected with MAS and 12 isolated tumors (10 GH-secreting adenomas, one toxic thyroid adenoma, and one hyperfunctioning adrenal adenoma).

Different inactivating mutations of the mineralocorticoid receptor in fourteen families affected by type I pseudohypoaldosteronism.

We have analyzed the human mineralocorticoid receptor (hMR) gene in 14 families with autosomal dominant or sporadic pseudohypoaldosteronism (PHA1), a rare form of mineralocorticoid resistance characterized by neonatal renal salt wasting and failure to thrive. Six heterozygous mutations were detected. Two frameshift mutations in exon 2 (insT1354, del8bp537) and one nonsense mutation in exon 4 (C2157A, Cys645stop) generate truncated proteins due to premature stop codons.