Multicentre comparison of free thyroid hormones immunoassays: the Immunocheck study.

Background: In order to evaluate whether there is still present a very large variability in measured values and analytical performance among different free thyroid (FT) hormone immunoassays, we considered the results derived from an External Quality Assessment (EQA) scheme, named Immunocheck.

Methods: The EQA Immonocheck study enrolled about 1000 participant laboratories, which measured the 54 quality control samples distributed in the three annual cycles (2007, 2008 and 2009). Participant laboratories produced a total of 30,476 results for FT3 and 31,351 for FT4, respectively.

Mutation spectrum of MLL2 in a cohort of Kabuki syndrome patients.

Background: Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histone methyl transferase MLL2 gene have been identified as its underlying cause.

Methods: Genomic DNAs were extracted from 62 index patients clinically diagnosed as affected by Kabuki syndrome.

Investigation of modifier genes within copy number variations in Rett syndrome.

MECP2 mutations are responsible for two different phenotypes in females, classical Rett syndrome and the milder Zappella variant (Z-RTT). We investigated whether copy number variants (CNVs) may modulate the phenotype by comparison of array-CGH data from two discordant pairs of sisters and four additional discordant pairs of unrelated girls matched by mutation type. We also searched for potential MeCP2 targets within CNVs by chromatin immunopreceipitation microarray (ChIP-chip) analysis.

Alport syndrome and leiomyomatosis: the first deletion extending beyond COL4A6 intron 2.

Alport syndrome (ATS) is a nephropathy characterized by the association of progressive hematuric nephritis with ultrastructural changes of the glomerular basement membrane (thinning, thickening, and splitting), sensorineural deafness, and variable ocular abnormalities (anterior lenticonus, macular flecks, and cataracts). The most common mode of transmission is X-linked inheritance, due to COL4A5 mutations. X-linked ATS is rarely associated with diffuse leiomyomatosis (DL), a benign hypertrophy of the visceral smooth muscle in gastrointestinal, respiratory, and female reproductive tracts.

Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations.

Rett syndrome (RTT) is characterized by a relatively specific clinical phenotype. We screened 152 individuals with RTT phenotype. A total of 22 different known MECP2 mutations were identified in 42 subjects (27.

Rett syndrome: revised diagnostic criteria and nomenclature.

Objective: Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was to revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials.

Association between primary open-angle glaucoma (POAG) and WDR36 sequence variance in Italian families affected by POAG.

Background/aims: To assess the involvement of WDR36 sequence variance in primary open-angle glaucoma (POAG) in Italian patients.

Methods: A cohort of 34 Italian families affected by POAG was analysed by denaturing high-performance liquid chromatography for mutation in the WDR36 gene. Among the 34 families enrolled, 25 were affected by high-tension glaucoma (HTG), four by juvenile open-angle glaucoma and one by normal tension glaucoma.

Epilepsy in Rett syndrome: clinical and genetic features.

Epilepsy often occurs in Rett syndrome and is considered a major problem. The aim of this study was to define the clinical features of epilepsy and the correlation between seizures and both genotype and clinical phenotype in the Rett population. One hundred sixty-five patients with Rett syndrome referred to four Italian centers were recruited.

High frequency of COH1 intragenic deletions and duplications detected by MLPA in patients with Cohen syndrome.

Cohen syndrome is a rare, clinically variable autosomal recessive disorder characterized by mental retardation, postnatal microcephaly, facial dysmorphisms, ocular abnormalities and intermittent neutropenia. Mutations in the COH1 gene have been found in patients from different ethnic origins. However, a high percentage of patients have only one or no mutated allele.

3.2 Mb microdeletion in chromosome 7 bands q22.2-q22.3 associated with overgrowth and delayed bone age.

We report a patient with mental retardation, epilepsy, overgrowth, delayed bone age, peculiar facial features, corpus callosum hypoplasia, enlarged cisterna magna and right cerebellar hypoplasia. Array-CGH analysis revealed the presence of a de novo 3.2 Mb interstitial deletion of the long arm of chromosome 7 involving bands q22.

Intellectual disability, midface hypoplasia, facial hypotonia, and Alport syndrome are associated with a deletion in Xq22.3.

Alport syndrome with intellectual disability (ID) is a contiguous gene deletion syndrome involving several genes on Xq22.3 including COL4A5 and ACSL4. We report on a family with two males with this disorder and a Xq22.

EEG features and epilepsy in MECP2-mutated patients with the Zappella variant of Rett syndrome.

Objective: To assess the presence/absence of peculiar EEG features and epilepsy in MECP2-mutated Rett patients with the Zappella-Rett variant (Z-RTT) also known as preserved speech variant.

Methods: Retrospective analysis of 16 (age 19.4+/-8.

Partial silencing of methyl cytosine protein binding 2 (MECP2) in mesenchymal stem cells induces senescence with an increase in damaged DNA.

DNA methylation is an epigenetic modification that occurs almost exclusively on CpG dinucleotides. MECP2 is a member of a family of proteins that preferentially bind to methylated CpGs. We analyzed the contribution of MECP2 to the physiology of mesenchymal stem cells (MSCs).

Unmasking of a Recessive SCARF2 Mutation by a 22q11.12 de novo Deletion in a Patient with Van den Ende-Gupta Syndrome.

Van den Ende-Gupta syndrome (VDEGS) is a congenital condition characterized by craniofacial and skeletal manifestations, specifically blepharophimosis, malar and maxillary hypoplasia, distinctive nose, arachnocamptodactyly, and long slender bones of the hands and feet. To date, only 24 patients have been described. It is generally thought that the syndrome is transmitted by an autosomal recessive mode of inheritance, although evidence for genetic heterogeneity has recently been presented.

The first Italian family with tibial muscular dystrophy caused by a novel titin mutation.

Tibial muscular dystrophy (TMD) or Udd myopathy is an autosomal dominant distal myopathy with late onset, at first described in the Finnish population. We report here the first Italian cases of TTN mutated titinopathy. The proband, a 60 year-old female, had the first muscular signs at the age of 59 years, with difficulty in walking and right foot drop.

Novel FOXG1 mutations associated with the congenital variant of Rett syndrome.

Background: Rett syndrome is a severe neurodevelopmental disorder representing one of the most common genetic causes of mental retardation in girls. The classic form is caused by MECP2 mutations. In two patients affected by the congenital variant of Rett we have recently identified mutations in the FOXG1 gene encoding a brain specific transcriptional repressor, essential for early development of the telencephalon.

Variation in novel exons (RACEfrags) of the MECP2 gene in Rett syndrome patients and controls.

The study of transcription using genomic tiling arrays has lead to the identification of numerous additional exons. One example is the MECP2 gene on the X chromosome; using 5'RACE and RT-PCR in human tissues and cell lines, we have found more than 70 novel exons (RACEfrags) connecting to at least one annotated exon..

Leukoencephalopathy in 21-beta hydroxylase deficiency: report of a family.

21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia, an autosomal recessive disorder characterized by impaired synthesis of cortisol from cholesterol by the adrenal cortex. Subclinical involvement of brain white matter has been reported in subjects with congenital adrenal hyperplasia. Here we report a woman with a genetically assessed classic congenital adrenal hyperplasia and brain white matter abnormalities.

Early-onset seizure variant of Rett syndrome: definition of the clinical diagnostic criteria.

Background: Rett syndrome is a severe neurodevelopmental disorder affecting almost exclusively females. Among Rett clinical variants, the early-onset seizure variant describes girls with early onset epilepsy and it is caused by mutations in CDKL5.

Methods: Four previously reported girls and five new cases with CDKL5 mutation, ranging from 14 months to 13 years, were evaluated by two clinical geneticists, classified using a severity score system based on the evaluation of 22 different clinical signs and compared with 128 classic Rett and 25 Zappella variant MECP2-mutated patients, evaluated by the same clinical geneticists.

A 9.3 Mb microdeletion of 3q27.3q29 associated with psychomotor and growth delay, tricuspid valve dysplasia and bifid thumb.

We describe a de novo 3q27.3q29 deletion in a 2.5-year-old female patient with developmental and growth delay, dysmorphic facial features, mild tricuspid valve dysplasia, bifid thumb, clinodactyly of the 2nd toe bilaterally and scoliosis.

14q12 Microdeletion syndrome and congenital variant of Rett syndrome.

Only two patients with 14q12 deletion have been reported to date. Here, we describe an additional patient with a similar deletion in order to improve the clinical delineation of this new microdeletion syndrome. The emerging phenotype is characterized by a Rett-like clinical course with an almost normal development during the first months of life followed by a period of regression.

Refinement of the 12q14 microdeletion syndrome: primordial dwarfism and developmental delay with or without osteopoikilosis.

In their studies on the molecular basis of osteopoikilosis, Menten et al have identified three individuals with microdeletions on chromosome 12q14.4, which removed several genes including LEMD3, the osteopoikilosis gene. In addition to osteopoikilosis, affected individuals had growth retardation and developmental delay.