Gandin I.,University of Trieste |
Faletra F.,Institute for Maternal and Child Health |
Carella M.,Medical Genetics Unit |
Pecile V.,Institute for Maternal and Child Health |
And 10 more authors.
Genetics in Medicine | Year: 2015
The harmful effects of inbreeding are well known by geneticists, and several studies have already reported cases of intellectual disability caused by recessive variants in consanguineous families. Nevertheless, the effects of inbreeding on the degree of intellectual disability are still poorly investigated. Here, we present a detailed analysis of the homozygosity regions in a cohort of 612 patients with intellectual disabilities of different degrees.Methods:We investigated (i) the runs of homozygosity distribution between syndromic and nonsyndromic ID (ii) the effect of runs of homozygosity on the ID degree, using the intelligence quotient score.Results:Our data revealed no significant differences in the first analysis; instead we detected significantly larger runs of homozygosity stretches in severe ID compared to nonsevere ID cases (P = 0.007), together with an increase of the percentage of genome covered by runs of homozygosity (P = 0.03).Conclusion:In accord with the recent findings regarding autism and other neurological disorders, this study reveals the important role of autosomal recessive variants in intellectual disability. The amount of homozygosity seems to modulate the degree of cognitive impairment despite the intellectual disability cause. © American College of Medical Genetics and Genomics.
Helsmoortel C.,University of Antwerp |
Vulto-Van Silfhout A.T.,Radboud University Nijmegen |
Coe B.P.,University of Washington |
Coe B.P.,Howard Hughes Medical Institute |
And 27 more authors.
Nature Genetics | Year: 2014
Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities, a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile-X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in next-generation sequencing, for the large majority of cases no molecular diagnosis can be established. Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD-associated genes known to date. © 2014 Nature America, Inc.
Concolino D.,University of Catanzaro |
Iembo M.A.,University of Catanzaro |
Moricca M.T.,University of Catanzaro |
Rapsomaniki M.,University of Catanzaro |
And 5 more authors.
European Journal of Medical Genetics | Year: 2012
We report a new case of 8q interstitial duplication in a patient with dysmorphic features, umbilical hernia, cryptorchidism, short stature, congenital heart defect and mild mental retardation (MR). Chromosome analysis with high resolution QFQ bands showed 46,XY, 8q+, which was interpreted as a partial duplication of the distal long arm of chromosome 8 (q22 → qter). This chromosomal aberration was further characterized using fluorescence in situ hybridization (FISH) analyses with multiple DNA probes and array-CGH (Comparative Genomic Hybridization) experiment which demonstrated a de novo direct duplication (8)(q22.2-q24.3). We have compared this case with other partially trisomic 8q patients reported in literature and highlighted the common clinical features in 8q22-8q24 duplication syndrome. © 2011.
Romano C.,Unit of Pediatrics and Medical Genetics
Monographs in Human Genetics | Year: 2010
Mental retardation (MR), also known as intellectual disability, is one of the most common neuropsychiatric disorders in infants, children and adolescents. Its prevalence in the general population is usually reported in the 1-3% range. Understanding its cause gives important benefits to the patient, his/her family, and the general practitioner. There is a diagnostic triad made up of intellectual functioning significantly below the mean, concurrent deficiencies in at least 2 areas of adaptive functioning, and onset before 18 years. This paves the way for MR to be scaled in different degrees and allows the distinction between intellectual and adaptive performance, and between adaptive and maladaptive behaviour. The suggested clinical approach comprises 6 main steps: 1) Family history, 2) personal history, 3) physical examination, 4) clinical diagnosis, 5) imaging and laboratory diagnostics, 6) diagnostic synthesis and follow-up. New technologies, such as array comparative genomic hybridisation (aCGH), are currently making a huge impact, shifting in many instances from a phenotype-first to a genotype-first approach. This emphasizes the need for a close collaboration between clinicians and laboratory professionals. The aim of clinical evaluation is to provide the best care for the patient, which relies on habilitation and counselling for his/her family. Copyright © 2010 S. Karger AG, Basel.
Romano C.,Unit of Pediatrics and Medical Genetics |
Schepis C.,Unit of Dermatology
The Scientific World Journal | Year: 2012
PTEN gene is considered one of the most mutated tumor suppressor genes in human cancer, and it's likely to become the first one in the near future. Since 1997, its involvement in tumor suppression has smoothly increased, up to the current importance. Germline mutations of PTEN cause the PTEN hamartoma tumor syndrome (PHTS), which include the past-called Cowden, Bannayan-Riley-Ruvalcaba, Proteus, Proteus-like, and Lhermitte-Duclos syndromes. Somatic mutations of PTEN have been observed in glioblastoma, prostate cancer, and brest cancer cell lines, quoting only the first tissues where the involvement has been proven. The negative regulation of cell interactions with the extracellular matrix could be the way PTEN phosphatase acts as a tumor suppressor. PTEN gene plays an essential role in human development. A recent model sees PTEN function as a stepwise gradation, which can be impaired not only by heterozygous mutations and homozygous losses, but also by other molecular mechanisms, such as transcriptional regression, epigenetic silencing, regulation by microRNAs, posttranslational modification, and aberrant localization. The involvement of PTEN function in melanoma and multistage skin carcinogenesis, with its implication in cancer treatment, and the role of front office in diagnosing PHTS are the main reasons why the dermatologist should know about PTEN. © 2012 Corrado Romano and Carmelo Schepis.