1,720,994 research outputs found
Hermansky-Pudlak syndrome
No full textA 1-year-old female child suffering from nystagmus and abnormal head posture (AHP) was presented by the parents in our clinic. The family history revealed the presence of von Willebrand's disease in both parents. General examination showed a female child with light blond colored skin accompanied by black-haired parents. Physical and ophthalmic examination revealed nystagmus, AHP and oculocutaneous albinism. The molecular genetic analysis showed a mutation in the HPS-1 gene which confirmed the suspected diagnosis of Hermansky-Pudlak syndrome (HPS). Of clinical significance, patients with HPS commonly have hemorrhagic diathesis, granulomatous colitis or restrictive lung fibrosis. A detailed full medical history, ophthalmic examination as well as genetic analyses are essential in establishing the diagnosis of HPS. Treatment includes correcting refraction anomalies with spectacles or contact lenses, prescription of tinted glasses or surgical correction of the AHP. An internal medical consultation is also necessary for the management of other associated symptoms, such as hemorrhagic diathesis
Characterization of five novel large deletions causing hereditary haemorrhagic telangiectasia
No full textUsing quantitative real-time polymerase chain reaction (QRT-PCR), molecular genetic analysis was carried out for endoglin (ENG) and activin A receptor type II-like kinase 1 (ACVRL1/ALK1) gene rearrangements in a group of 45 clinically confirmed hereditary haemorrhagic telangiectasia (HHT) families with negative direct sequencing results. We detected five large novel deletions, four in the ALK1 gene and one in the ENG gene. In two families, the whole ALK1 gene was deleted. One of these two deletions spanned at least 216 kb and included five neighbouring genes (LOC728503, ANKRD33, ACVR1B, GRASP, and NR4A1). The lack of additional symptoms in the patient carrying this large deletion indicates that heterozygous loss of these five genes has no obvious phenotypical effect. To our knowledge, this is the first report on whole ALK1 gene deletions in HHT patients. We rescreened our 45 families for large rearrangements using the multiplex ligation-dependent probe amplification (MLPA) method. No discrepancies between the results of QRT-PCR and MLPA were found. Our present work proves QRT-PCR as a reliable and sensitive method. Thus, our study supports that screening for large rearrangements should be considered to improve the genetic analysis in HHT patients with no apparent mutations in ALK1 and ENG using direct sequencing
Microduplication of 3p26.3 in Nonsyndromic Intellectual Disability Indicates an Important Role of CHL1 for Normal Cognitive Function
No full textTerminal deletions of chromosome 3p26.3 confined to the CHL1 gene have previously been described in children with intellectual disability and epilepsy. Here, we report for the first time, a 3p26.3 duplication including only the CHL1 gene in an intellectually disabled girl with epilepsy. The penetrance of both deletions and duplications in 3p26.3 is reduced because all chromosomal imbalances were inherited from healthy parents. Further studies are needed to specify the pathogenic mechanism of 3p26.3 imbalances and to estimate recurrence risks in genetic counseling. However, the description of both deletions and duplications of chromosome 3p26.3 in nonsyndromic intellectual disability suggests that CHL1 is a dosage-sensitive gene with an important role for normal cognitive development
A newborn with hereditary haemorrhagic telangiectasia and an unusually severe phenotype
No full textHereditary haemorrhagic telangiectasia (HHT), associated with arteriovenous malformations, is a genetic disease of the vascular system with a frequency of approx. 1:10,000. Genetic diagnosis serves to identify individuals at risk of developing the disease and is a useful tool for genetic counselling purposes. Questions under study: Here we report on a child presenting severe arteriovenous malformations leading to heart failure. Her mother and grandmother present fewer symptoms of hereditary haemorrhagic telangiectasia. In this study we identify the cause of HHT in the family. Methods: Clinical examination, PCR, DNA sequencing, quantitative PCR, Southern blot, x-ray, ultrasound, cardiac catheterisation and angiocardiography. Results: Initially the sequence variant in c.392C > T in the endoglin gene was detected in the grandmother, but not in other affected family members. Further analyses revealed a deletion of exon 1 of endoglin, segregating with the phenotype. Conclusions: This report points out the need for careful evaluation of molecular genetic findings, particularly in diseases with highly variable phenotype
Normal intelligence and premature ovarian failure in an adult female with a 7.6 Mb de novo terminal deletion of chromosome 9p
No full textDistal deletion 9p is associated with gonadal dysfunction in XY individuals. Little is known about the gonadal function and fertility of XX females with this condition. We report on an affected 31-year-old infertile woman presenting with premature ovarian failure, mild dysmorphic features, a history of mild developmental delay and an otherwise normal female phenotype. Cytogenetic analysis showed a deletion 9p with the karyotype 46, XX, del(9)(p23-24) in lymphocytes. The subsequent oligonucleotide array-based CGH analysis with genomic DNA from peripheral blood revealed a terminal deletion of approximately 7.6 Mb. SNP microarray analyses of the patient and her unaffected parents confirmed the deletion breakpoint and revealed a de novo mutation of paternal origin. This is apparently the first description of an adult woman with a cytogenetically visible terminal deletion of chromosome 9p. The fertility problems observed in this patient complement earlier findings in prepubertal and pubertal 46, XX-girls with 9p deletions, who displayed a phenotype ranging from primary ovarian dysfunction and mild gonadotropin hyperresponses to positive menses. DMRT1 is hemizygous in our patient. We discuss the role of DMRT1 in female gonadal development. (C) 2013 Elsevier Masson SAS. All rights reserved.Wellcome Trus
Multifocal Capillary Malformations Due to RASA1 Mutation Misdiagnosed as Cutaneous Mastocytosis
No full textA Family with an Inverted Tandem Duplication 5q22.1q23.2
No full textHere, we report a 3-year-old boy with short stature, developmental delay and mild facial dysmorphic signs. Karyotype analysis and array-CGH revealed a pure duplication 5q22.1q23.2 with a length of 14.25 Mb. As demonstrated by multicolor-fluorescence in situ hybridization, the duplicated segment was orientated in an inverted tandem manner. One of the 2 older half-brothers of the index patient was intellectually disabled and showed short stature as well. The mother of the siblings was only 149 cm in height. The affected half-brother as well as the mother of the siblings were tested positive for the same duplication. Duplications of the long arm of chromosome 5 are rare. There are 16 reported cases of different 5q segments with a pure duplication and no additional chromosomal imbalance. In order to refine the 5q-duplication phenotype, reported cases were recently classified in 3 groups on the basis of clinical findings and the involved chromosome segments. However, our case does not fit in any of these groups but is placed in the interjacent chromosomal area between 2 of these groups. Overall, this is the second reported family with a duplication of 5q22.1q23.2 and both families share phenotypic features like short stature, facial dysmorphic signs and speech delay. The reported family provides further information for delineating phenotype-genotype correlations of pure duplications of the 5q region. Copyright (C) 2012 S. Karger AG, Base
Discordant phenotype in monozygotic twins with mosaic trisomy 12p in lymphocytes
No full textWe report on monochorionic diamniotic male twins discordant for the trisomy 12p syndrome. Trisomy 12p mosaicism with a supernumerary der(12)(pter > q12) was detected in approximately 50% of lymphocytes in both children. Fluorescence in situ hybridisation (FISH) revealed a high grade mosaicism of approximately 77% trisomy 12p cells in buccal smear and 85% in hair follicles in the affected twin, while in the normal developing brother an additional 12p chromosome fragment could not be detected in those tissues. Instead, in 3% of buccal smear and hair follicle cells a minute supernumerary marker chromosome comprising central portions of chromosome 12 was observed. Trisomy 12p mosaicism, confined to the lymphocytes of the unaffected twin, may be due to prenatal twin-to-twin transfusion, explaining the conspicuously discordant clinical phenotype. We discuss the possible sequence of events leading to the cytogenetic findings and compare the clinical phenotype presented in the affected twin with other cases of trisomy 12p and tetrasomy 12p (Pallister-Killian syndrome). (c) 2012 Elsevier Masson SAS. All rights reserved
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