21 research outputs found
Investigation of FANCA mutations in greek patients
Background: Fanconi anemia (FA) is a rare genetic disease characterized by considerable heterogeneity. Fifteen subtypes are currently recognised and deletions of the Fanconi anemia complementation group A (FANCA) gene account for more than 65% of FA cases. We report on the results from a cohort of 166 patients referred to the Department of Medical Genetics of Athens University for genetic investigation after the clinical suspicion of FA. Materials and Methods: For clastogen-induced chromosome damage, cultures were set up with the addition of mitomycin C (MMC) and diepoxybutane (DEB), respectively. Following a positive cytogenetic result, molecular analysis was performed to allow identification of causative mutations in the FANCA gene. Results: A total of 13/166 patients were diagnosed with FA and 8/13 belonged to the FA-A subtype. A novel point mutation was identified in exon 26 of FANCA gene. Conclusion: In our study 62% of FA patients were classified in the FA-A subtype and a point mutation in exon 26 was noted for the first time
A Clinical Study of Sotos Syndrome Patients With Review of the Literature
Sotos syndrome is characterized by tall stature, advanced bone age,
typical facial abnormalities, and developmental delay. The associated
gene is NSD1. The study involved 22 patients who fulfilled the clinical
criteria. Phenotypic characteristics, central nervous system findings,
and cardiovascular and urinary tract abnormalities were evaluated.
Meta-analysis on the incidence of cardinal clinical manifestations from
the literature was also performed. Macrocephaly was present in all
patients. Advanced bone age was noted in 14 of 22 patients (63%), and
its incidence presented significant statistical difference in the
meta-analysis of previous studies. Some patients had serious clinical
manifestations, such as congenital heart defects, dysplastic kidneys,
psychosis, and leukemia. Clinical and laboratory examinations should be
performed to prevent and manage any unusual medical aspect of the
syndrome. Facial gestalt and macrocephaly, rather than advanced bone
age, are the strongest indications for clinical diagnosis. (C) 2009 by
Elsevier Inc. All rights reserved
Phenotypic and Genotypic Variability in Four Males With MECP2 Gene Sequence Aberrations Including a Novel Deletion
The MECP2 gene mutations cause Rett syndrome (RTT) (OMIM: 312750), an
X-linked dominant disorder primarily affecting girls. Until RTT was
considered lethal in males, although now approximately 60 cases have
been reported. Males with MECP2 mutations present with a broad spectrum
of phenotypes ranging from neonatal encephalopathy to nonsyndromic
mental retardation (MR). Four boys (aged, 3-11 y) were evaluated for MR.
Patient I had autistic features. Patients 2 and 3 were brothers both
presenting with psychomotor delay. Patient 4 showed dysmorphic features
and behavioral problems reminiscent of FXS. All patients had a normal
46, XY karyotype and three were tested for FXS with negative results.
MECP2 gene analysis of exons 3 and 4 was performed using methods based
on the PCR, including Enzymatic Cleavage Mismatched Analysis (ECMA) and
direct sequencing. Patient I presented somatic mosaicism for the classic
RTT p.R106W mutation and patient 4 carried the p.T203M polymorphism.
Analysis of the mothers in both cases revealed normal DNA sequences.
Patients 2 and 3 had a novel deletion (c.1140del86) inherited from their
unaffected mother. MECP2 gene mutations may be considered a rare cause
of MR in males although great phenotypic variation hinders
genotype-phenotype correlation. (Pediatr Res 67: 551-556, 2010