Dataset Information

Kenny-Caffey syndrome is part of the CATCH 22 haploinsufficiency cluster.

ABSTRACT: We report four sibs with Kenny-Caffey syndrome in a consanguineous Bedouin family. The first two died in the neonatal period while the remaining affected brother and sister had all the characteristic clinical, biochemical, and radiological abnormalities of the syndrome. These included severe pre- and postnatal growth retardation, cortical thickening of the tubular bones with medullary stenosis, eye abnormalities, facial dysmorphism, hypocalcaemia, and low levels of parathyroid hormone. The children also showed intracranial calcification, impaired neutrophil phagocytosis, increased proportion of B lymphocytes, reduced CD4 and CD8 subpopulations of T lymphocytes, and inhibited transformation in response to Candida antigen. Fluorescence in situ hybridisation (FISH) was applied to blood lymphocyte metaphase spreads from these two Bedouin sibs and their parents using probe D22S75 (Oncor), specific for the DiGeorge critical region on chromosome 22q11.2. The presence of 22q11.2 haploinsufficiency was identified in the affected sibs, which was transmitted from the phenotypically normal mother. The present report widens the spectrum of CATCH 22 microdeletion to accommodate Kenny-Caffey syndrome.

SUBMITTER: Sabry MA

PROVIDER: S-EPMC1051183 | biostudies-other | 1998 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Kenny-Caffey syndrome is part of the CATCH 22 haploinsufficiency cluster.

Sabry M A MA Zaki M M Abul Hassan S J SJ Ramadan D G DG Abdel Rasool M A MA al Awadi S A SA al Saleh Q Q

Journal of medical genetics 19980101 1

We report four sibs with Kenny-Caffey syndrome in a consanguineous Bedouin family. The first two died in the neonatal period while the remaining affected brother and sister had all the characteristic clinical, biochemical, and radiological abnormalities of the syndrome. These included severe pre- and postnatal growth retardation, cortical thickening of the tubular bones with medullary stenosis, eye abnormalities, facial dysmorphism, hypocalcaemia, and low levels of parathyroid hormone. The child ...[more]

PMID: 9475091

Similar Datasets

Project description:BackgroundNeuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system and is a major therapeutic challenge. Several screening tools have been developed to help physicians detect patients with neuropathic pain. These have typically been validated in populations pre-stratified for neuropathic pain, leading to a so called "Catch-22 situation:" "a problematic situation for which the only solution is denied by a circumstance inherent in the problem or by a rule". The validity of screening tools needs to be proven in patients with pain who were not pre-stratified on basis of the target outcome: neuropathic pain or non-neuropathic pain. This study aims to assess the validity of the Dutch PainDETECT (PainDETECT-Dlv) in a large population of patients with chronic pain.MethodsA cross-sectional multicentre design was used to assess PainDETECT-Dlv validity. Included where patients with low back pain radiating into the leg(s), patients with neck-shoulder-arm pain and patients with pain due to a suspected peripheral nerve damage. Patients' pain was classified as having a neuropathic pain component (yes/no) by two experienced physicians ("gold standard"). Physician opinion based on the Grading System was a secondary comparison.ResultsIn total, 291 patients were included. Primary analysis was done on patients where both physicians agreed upon the pain classification (n?=?228). Compared to the physician's classification, PainDETECT-Dlv had a sensitivity of 80% and specificity of 55%, versus the Grading System it achieved 74 and 46%.ConclusionDespite its internal consistency and test-retest reliability the PainDETECT-Dlv is not an effective screening tool for a neuropathic pain component in a population of patients with chronic pain because of its moderate sensitivity and low specificity. Moreover, the indiscriminate use of the PainDETECT-Dlv as a surrogate for clinical assessment should be avoided in daily clinical practice as well as in (clinical-) research. Catch-22 situations in the validation of screening tools can be prevented by not pre-stratifying the patients on basis of the target outcome before inclusion in a validation study for screening instruments.Trial registrationThe protocol was registered prospectively in the Dutch National Trial Register: NTR 3030 .

Project description:Purpose: 5A3+/del mice, which have a heterozygous germ line deletion of a 2-Mb interval of chromosome band 5A3 syntenic to a commonly deleted segment of human 7q22, exhibit hematopoietic stem cell (HSC) abnormalities that may contribute to myelodysplastic syndrome (MDS) pathogenesis. These defects are cell autonomous. The goal of this study is to compare transcriptome profiling (RNA-seq) data obtained from HSC and multipotent progenitors (MPP) isolated from 5A3+/del mice and their wildtype littermates, in order to identify differentially expressed genes and pathways that may contribute to the phenotype. Methods: Total RNA was isolated from CD150hi-HSC, CD150lo-HSC and CD150neg-MPP from wildtype and 5A3+/del mice. 10ng of total RNA was converted into double-stranded cDNA using the Ovation RNA Amplification System V2 (NuGen, CA), and the amplified cDNA products were then used to generate RNA-seq libraries using the TruSeq RNA Sample Preparation Kit v2 reagents (Illumina, CA) with 10 PCR amplification cycles. Library quality and quantity were assessed by the Agilent DNA1000 Chip (Agilent, CA) and qPCR (Kappa Biosystems Inc, MA). 10 pM of each library was sequenced using Illumina SBS chemistry at 2 x 100 bp reads on the HiSeq2000 (Illumina®, CA). The RNA-Seq paired-end reads were mapped to the mouse mm9 genome using an in-house mapping and quality assessment pipeline. The expression of each gene was estimated by the mean coverage of the highest-covered coding exon. Genes with low expression level (<10) across all samples were filtered out, followed by quantile normalization. Differential expression analysis was performed using limma with estimation of false-discovery rate. Gene Set Enrichment Analysis was used to assess pathway enrichment. Results:Transcriptome (RNA-Seq) and Taqman quantitative real-time PCR analyses revealed a ~50% reduction in the expression of multiple genes and of the long intergenic non-coding RNA 503142E22Rik within the 5A3 interval in mutant HSC and MPP. Gene Set Enrichment Analysis (GSEA) of the RNA-Seq data from 5A3+/del HSCs further demonstrated reduced expression of multiple gene sets related to oxidative phosphorylation (OXPHOS) that are similarly down-regulated in the early stages of human therapy-induced MDS and AML. Conclusions: Our study revealed that genes involved in OXPHOS were down-regulated in 5A3+/del HSC, and this finding provided novel insights into the impact of chromosome 7 deletions on the pathogenesis of MDS. Transcriptome profiling (RNA-seq) data of HSC and MPP isolated from 5A3+/del mice and their wildtype littermates were generated by sequencing, in quintuplicate, using Illumina SBS chemistry at 2 x 100 bp reads on the HiSeq2000 (Illumina®, CA)

Dataset Information

Kenny-Caffey syndrome is part of the CATCH 22 haploinsufficiency cluster.

Publications

Kenny-Caffey syndrome is part of the CATCH 22 haploinsufficiency cluster.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets