Search results for "Deletion syndrome"
showing 10 items of 18 documents
Clinical and molecular characterization of 112 single-center patients with Neurofibromatosis type 1.
2018
Abstract Background The aim of this retrospective study was to define clinical and molecular characteristics of a large sample of neurofibromatosis type 1 (NF1) patients, as well as to evaluate mutational spectrum and genotype-phenotype correlation. NF1 is a relatively common neurogenetic disorder (1:2500–1:3000 individuals). It is caused by mutations of the NF1 gene on chromosome 17ql1.2, with autosomal dominant pattern of inheritance and wide phenotypical variability. Café-au-lait spots (CALs), cutaneous and/or subcutaneous neurofibromas (CNFs/SCNFs), skinfold freckling, skeletal abnormalities, Lisch nodules of the iris and increased risk of learning and intellectual disabilities, as well…
Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature
2016
Item does not contain fulltext Verheij syndrome, also called 8q24.3 microdeletion syndrome, is a rare condition characterized by ante- and postnatal growth retardation, microcephaly, vertebral anomalies, joint laxity/dislocation, developmental delay (DD), cardiac and renal defects and dysmorphic features. Recently, PUF60 (Poly-U Binding Splicing Factor 60 kDa), which encodes a component of the spliceosome, has been discussed as the best candidate gene for the Verheij syndrome phenotype, regarding the cardiac and short stature phenotype. To date, only one patient has been reported with a de novo variant in PUF60 that probably affects function (c.505C>T leading to p.(His169Tyr)) associated wi…
Jacobsen syndrome and neonatal bleeding: report on two unrelated patients
2021
Abstract Introduction In 1973, Petrea Jacobsen described the first patient showing dysmorphic features, developmental delay and congenital heart disease (atrial and ventricular septal defect) associated to a 11q deletion, inherited from the father. Since then, more than 200 patients have been reported, and the chromosomal critical region responsible for this contiguous gene disorder has been identified. Patients’ presentation We report on two unrelated newborns observed in Italy affected by Jacobsen syndrome (JBS, also known as 11q23 deletion). Both patients presented prenatal and postnatal bleeding, growth and developmental delay, craniofacial dysmorphisms, multiple congenital anomalies, a…
SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in fem…
2021
Contains fulltext : 231702.pdf (Publisher’s version ) (Closed access) Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals…
Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III
2000
Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated p…
Wilms' tumor in patients with 9q22.3 microdeletion syndrome suggests a role for PTCH1 in nephroblastomas
2012
Nephroblastoma (Wilms' tumor; WT) is the most common renal tumor of childhood. To date, several genetic abnormalities predisposing to WT have been identified in rare overgrowth syndromes. Among them, abnormal methylation of the 11p15 region, GPC3 and DIS3L2 mutations, which are responsible for Beckwith-Wiedemann, Simpson-Golabi-Behmel and Perlman syndromes, respectively. However, the underlying cause of WT remains unknown in the majority of cases. We report three unrelated patients who presented with WT in addition to a constitutional 9q22.3 microdeletion and dysmorphic/overgrowth syndrome. The size of the deletions was variable (ie, from 1.7 to 8.9 Mb) but invariably encompassed the PTCH1 …
Interstitial deletions of chromosome 1p: novel 1p31.3p22.2 microdeletion in a newborn with craniosynostosis, coloboma and cleft palate, and review of…
2022
Abstract Background Rearrangements of unstable DNA sequences may alter the structural integrity or the copy number of dose-sensitive genes, resulting in copy number variations. They may lead more frequently to deletions, in addition to duplications and/or inversions, which are the underlying pathogenic mechanism of a group of conditions known as genomic disorders (or also contiguous gene syndromes). Interstitial deletions of the short arm of chromosome 1 are rare, and only about 30 patients have been reported. Their clinical features are variable, in respect of the extent of the deleted region. They include global developmental delay, central nervous system (CNS) malformations, craniosynost…
Heterozygous HMGB1 loss-of-function variants are associated with developmental delay and microcephaly
2021
International audience; 13q12.3 microdeletion syndrome is a rare cause of syndromic intellectual disability. Identification and genetic characterization of patients with 13q12.3 microdeletion syndrome continues to expand the phenotypic spectrum associated with it. Previous studies identified four genes within the approximately 300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 and HMGB1. To date, no patients carrying a sequence-level variant or a single gene deletion in HMGB1 or KATNAL1 have been described. Here we report six patients with loss-of-function variants involving HMGB1 and who had phenotypic features similar to the previously described 13q12.3 m…
Interstitial deletion of chromosome 2p15-16.1: Report of two patients and critical review of current genotype–phenotype correlation
2011
Abstract We report two individuals with developmental delay and dysmorphic features, in whom array-based comparative genomic hybridization (array CGH) led to the identification of a 2p15p16.1 de novo deletion. In the first patient (Patient 1) a familial deletion of 6q12, inherited from her father, was also detected. In the second patient (Patient 2) in addition to the 2p15p16.1 microdeletion a de novo deletion in Xq28 was detected. Both individuals shared dysmorphic features and developmental delay with the six reported patients with a 2p15p16.1 microdeletion described in medical literature. Conclusion: in the first patient a 642 kb 2p16.1 deletion (from 60.604 to 61.246 Mb), and a 930 kb 6…
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…