Search results for "deletion"

Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

2013

CCR5 Proinflammatory Allele in Prostate Cancer Risk

2009

Prostate cancer (PCa) is the most common malignant neoplasm in older men in Western countries. The number of affected older men is increasing. Therefore, strategies for prevention of prostate cancer are crucial. To this purpose it is essential to know the mechanisms involved in development and progression of this malignancy. Recently, an increasing body of genetic and epidemiological studies proposed new hypotheses for prostate carcinogenesis. It has been suggested that genetic factors as well as exposure to environmental factors such as infectious agents, dietary carcinogens, and hormonal imbalances participate in PCa development. Besides, chronic inflammation plays a key role in PCa. Taki…

Clinical Significance of Rare Copy Number Variations in Epilepsy A Case-Control Survey Using Microarray-Based Comparative Genomic Hybridization

2012

Objective To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy. Design Prospective cohort study. Setting Epilepsy centers in Italy. Patients Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization. Main Outcomes Measures Identification of copy number variations (CNVs) and gene enrichment. Results Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P = .26). The CNVs identified in patients were larger (P = …

Rare variants in the genetic background modulate cognitive and developmental phenotypes in individuals carrying disease-associated variants

2019

Purpose: To assess the contribution of rare variants in the genetic background toward variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive variants. Methods: We analyzed quantitative clinical information, exome sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated variants. Results: The number of rare likely deleterious variants in functionally intolerant genes (“other hits”) correlated with expression of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in autism probands carrying gene-disruptive variants (n=184, p=0.03) compared with thei…

Identification of the novel D297fsX318 PINK1 mutation and phenotype variation in a family with early-onset Parkinson's disease

2008

Herein we first describe a novel homozygous single nucleotide deletion in PINK1 exon 4 (889delG) which results in a loss of kinase domain on the PINK1 protein (D297fsX318). This mutation was identified in two brothers with early-onset Parkinson disease (EOPD) from a Sicilian consanguineous family. Of note, while one of the two patients developed mental deterioration and psychiatric problems, the other showed no cognitive decline. The present study supports the view that PINK1 is a pathogenic gene in some Italian families with EOPD and contributes to define the PINK1-associated phenotype. Herein we first describe a novel homozygous single nucleotide deletion in PINK1 exon 4 (889delG) which r…

Delineation of the 3p14.1p13 microdeletion associated with syndromic distal limb contractures

2014

International audience; Distal limb contractures (DLC) represent a heterogeneous clinical and genetic condition. Overall, 20–25% of the DLC are caused by mutations in genes encoding the muscle contractile apparatus. Large interstitial deletions of the 3p have already been diagnosed by standard chromosomal analysis, but not associated with a specific phenotype. We report on four patients with syndromic DLC presenting with a de novo 3p14.1p13 micro-deletion. The clinical features associated multiple contractures, feeding problems, developmental delay, and intellectual disability. Facial dysmorphism was constant with low-set posteriorly rotated ears and blepharophimosis. Review of previously r…

Infant developmental profile of Crisponi syndrome due to compound heterozygosity for CRLF1 deletion.

2020

Crisponi syndrome/CISS1, is an autosomal recessive ciliary neurotrophic factor receptor (CNTFR)-related genodermatosis caused in 95% of cases by mutations in CRLF1 on chromosome 19p13. The CNTFR pathway is important for CNS development. Crisponi syndrome/ CISS1 can be suspected in the presence of the following clinical triad: camptodactyly with fisted hands, intermittent hyperthermia and muscular contractions with feeding difficulties.

A Paucisymptomatic Neuromuscular Disease Mimicking Type III 5q-SMA With Complex Rearrangements in the SMN Gene

2013

Spinal muscular atrophy is an autosomal-recessive neuromuscular disorder, causing progressive proximal weakness and atrophy of the voluntary muscles. More than 96% of the spinal muscular atrophy patients show a homozygous absence of exons 7 and 8, or exon 7 only, in SMN1, the telomeric copy of the SMN gene. We report a young male patient with neurogenic symptoms and sparse muscle fiber atrophy, suggestive of a mild form of type III spinal muscular atrophy. He was found to be a carrier of intragenic mutations in both copies of the SMN gene, exhibiting a homozygous duplication of exons 7 and 8 in SMN1 and a homozygous deletion of exon 8 as well as a heterozygous deletion of exon 7 in SMN2. H…

Further delineation of eye manifestations in homozygous 15q13.3 microdeletions including TRPM1: a differential diagnosis of ceroid lipofuscinosis.

2014

The 15q13.3 heterozygous microdeletion is a fairly common microdeletion syndrome with marked clinical variability and incomplete penetrance. The average size of the deletion, which comprises six genes including CHRNA7, is 1.5 Mb. CHRNA7 has been identified as the gene responsible for the neurological phenotype in this microdeletion syndrome. Only seven patients with a homozygous microdeletion that includes at least CHRNA7, and is inherited from both parents have been described in the literature. The aim of this study was to further describe the distinctive eye manifestations from the analysis in the three French patients diagnosed with the classical 1.5 Mb homozygous microdeletion. Patients…

Clinical features and follow-up in patients with 22q11.2 deletion syndrome

2014

Objective To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease. Study design A retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis. Results The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In…