BackgroundWolf–Hirschhorn syndrome (WHS) (OMIM 194190) is a multiple congenital anomalies/intelle... more BackgroundWolf–Hirschhorn syndrome (WHS) (OMIM 194190) is a multiple congenital anomalies/intellectual disability syndrome. It is caused by partial loss of genetic material from the distal portion of the short arm of chromosome.MethodsWe studied the phenotype–genotype correlation.ResultsWe present the clinical manifestations and cytogenetic results of 10 unrelated Egyptian patients with 4p deletions. Karyotyping, FISH and MLPA was performed for screening for microdeletion syndromes. Array CGH was done for two patients. All patients exhibited the cardinal clinical manifestation of WHS. FISH proved deletion of the specific WHS locus in all patients. MLPA detected microdeletion of the specific locus in two patients with normal karyotypes, while array CGH, performed for two patients, has delineated the extent of the deleted segments and the involved genes. LETM1, the main candidate gene for the seizure phenotype, was found deleted in the two patients tested by array CGH; nevertheless, o...
Introduction Corpus callosum (CC) is the main fiber bundle connecting the brain interhemispheric ... more Introduction Corpus callosum (CC) is the main fiber bundle connecting the brain interhemispheric white matter tracts. Abnormalities of CC may be isolated, or occur in association with other brain anomalies as a part of monogenic syndrome, with some inborn errors of metabolism or due to chromosomal abnormalities. Aim Detecting the prevalence and characteristics of chromosomal aberrations among patients with CC abnormalities in addition to determining the subsequent imperative diagnostic steps in order to reach a precise diagnosis. Patients and methods A total of 105 patients have been enrolled into this study. All patients were subjected to full history taking, thorough clinical examination, neuroimaging studies, psychological assessments, and cytogenetic studies including G-banding karyotyping and fluorescence in-situ hybridization analysis. Results The vast majority of the studied patients presented with developmental delay (74%). Intellectual disability was demonstrated in 50.4%. ...
Background 22q11.2 deletion syndrome (22q11.2 DS) is one of the most common genetic causes of lea... more Background 22q11.2 deletion syndrome (22q11.2 DS) is one of the most common genetic causes of learning disability. The aim of the study was to characterize genetically the individuals with clinical suspicion of 22q11.2 DS using sequential cytogenetic approach. Patients and methods The present study was conducted on 20 patients with features suggestive of 22q11.2 DS including cardiac, velopharyngeal, craniofacial, and other dysmorphic features. Cytogenetic and molecular analyses were performed by conventional karyotyping and fluorescence in-situ hybridization (FISH). Multiplex ligation-dependent probe amplification analysis (MLPA) was done for cases clinically suspected of being affected with 22q11.2 DS and showing no deletion by FISH. Results Conventional karyotyping revealed two (10%) cases and FISH analysis revealed four cases with deletion in the 22q11.2 region. No more cases were detected by MLPA analysis compared with FISH. Conclusion The diagnosis of 22q11.2 DS is primarily su...
Background Cornelia de Lange syndrome (CdLS) is a rare clinically and genetically heterogeneous d... more Background Cornelia de Lange syndrome (CdLS) is a rare clinically and genetically heterogeneous disease. Cardinal phenotypic manifestations include specific dysmorphic facial features, growth retardation, intellectual disability, and upper limb anomalies. Mutations in five genes including NIPBL, SMC1A, SMC3, RAD21, and HDAC8 are known to be responsible for the syndrome, with the NIPBL gene mutation being the most prevalent (~80%). This study aimed to report the clinical, cytogenetic, and molecular characterization of a patient with CdLS with a heterozygous novel exonic missense mutation of the NIPBL gene. Patients and methods We have studied a male patient of 9 years and 4 months of age who presented with features suggestive of CdLS. Thorough clinical examination, conventional cytogenetic analysis, and molecular study using direct Sanger sequencing were performed. Results Clinical examination favored the diagnosis of CdLS. Conventional cytogenetic analysis revealed a normal 46, XY k...
Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by dysmorphic fea... more Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by dysmorphic features, mental retardation, and congenital heart disease (CHD). MWS results from microdeletions of chromosome 2q23 or de novo SNVs involving the ZEB2 gene. Here, we report on an Egyptian MWS patient diagnosed by chromosomal microarray (CMA). A 1-year-old male child was referred to the CHD clinic, National Research Centre, presenting with dysmorphic features and CHD. The patient was referred to the human cytogenetics department for cytogenetic analysis and for screening of subtelomere rearrangements and microdeletion loci, using MLPA, and all revealed normal results. CMA revealed an interstitial 2.27-Mb microdeletion in chromosome 2q, involving the entire ZEB2 gene and other genes. This study emphasizes the significance of CMA in the detection of microdeletions/microduplications and as a screening tool in cases presenting with CHD and extracardiac manifestations. MWS should be suspected in...
BackgroundWolf–Hirschhorn syndrome (WHS) (OMIM 194190) is a multiple congenital anomalies/intelle... more BackgroundWolf–Hirschhorn syndrome (WHS) (OMIM 194190) is a multiple congenital anomalies/intellectual disability syndrome. It is caused by partial loss of genetic material from the distal portion of the short arm of chromosome.MethodsWe studied the phenotype–genotype correlation.ResultsWe present the clinical manifestations and cytogenetic results of 10 unrelated Egyptian patients with 4p deletions. Karyotyping, FISH and MLPA was performed for screening for microdeletion syndromes. Array CGH was done for two patients. All patients exhibited the cardinal clinical manifestation of WHS. FISH proved deletion of the specific WHS locus in all patients. MLPA detected microdeletion of the specific locus in two patients with normal karyotypes, while array CGH, performed for two patients, has delineated the extent of the deleted segments and the involved genes. LETM1, the main candidate gene for the seizure phenotype, was found deleted in the two patients tested by array CGH; nevertheless, o...
Introduction Corpus callosum (CC) is the main fiber bundle connecting the brain interhemispheric ... more Introduction Corpus callosum (CC) is the main fiber bundle connecting the brain interhemispheric white matter tracts. Abnormalities of CC may be isolated, or occur in association with other brain anomalies as a part of monogenic syndrome, with some inborn errors of metabolism or due to chromosomal abnormalities. Aim Detecting the prevalence and characteristics of chromosomal aberrations among patients with CC abnormalities in addition to determining the subsequent imperative diagnostic steps in order to reach a precise diagnosis. Patients and methods A total of 105 patients have been enrolled into this study. All patients were subjected to full history taking, thorough clinical examination, neuroimaging studies, psychological assessments, and cytogenetic studies including G-banding karyotyping and fluorescence in-situ hybridization analysis. Results The vast majority of the studied patients presented with developmental delay (74%). Intellectual disability was demonstrated in 50.4%. ...
Background 22q11.2 deletion syndrome (22q11.2 DS) is one of the most common genetic causes of lea... more Background 22q11.2 deletion syndrome (22q11.2 DS) is one of the most common genetic causes of learning disability. The aim of the study was to characterize genetically the individuals with clinical suspicion of 22q11.2 DS using sequential cytogenetic approach. Patients and methods The present study was conducted on 20 patients with features suggestive of 22q11.2 DS including cardiac, velopharyngeal, craniofacial, and other dysmorphic features. Cytogenetic and molecular analyses were performed by conventional karyotyping and fluorescence in-situ hybridization (FISH). Multiplex ligation-dependent probe amplification analysis (MLPA) was done for cases clinically suspected of being affected with 22q11.2 DS and showing no deletion by FISH. Results Conventional karyotyping revealed two (10%) cases and FISH analysis revealed four cases with deletion in the 22q11.2 region. No more cases were detected by MLPA analysis compared with FISH. Conclusion The diagnosis of 22q11.2 DS is primarily su...
Background Cornelia de Lange syndrome (CdLS) is a rare clinically and genetically heterogeneous d... more Background Cornelia de Lange syndrome (CdLS) is a rare clinically and genetically heterogeneous disease. Cardinal phenotypic manifestations include specific dysmorphic facial features, growth retardation, intellectual disability, and upper limb anomalies. Mutations in five genes including NIPBL, SMC1A, SMC3, RAD21, and HDAC8 are known to be responsible for the syndrome, with the NIPBL gene mutation being the most prevalent (~80%). This study aimed to report the clinical, cytogenetic, and molecular characterization of a patient with CdLS with a heterozygous novel exonic missense mutation of the NIPBL gene. Patients and methods We have studied a male patient of 9 years and 4 months of age who presented with features suggestive of CdLS. Thorough clinical examination, conventional cytogenetic analysis, and molecular study using direct Sanger sequencing were performed. Results Clinical examination favored the diagnosis of CdLS. Conventional cytogenetic analysis revealed a normal 46, XY k...
Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by dysmorphic fea... more Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by dysmorphic features, mental retardation, and congenital heart disease (CHD). MWS results from microdeletions of chromosome 2q23 or de novo SNVs involving the ZEB2 gene. Here, we report on an Egyptian MWS patient diagnosed by chromosomal microarray (CMA). A 1-year-old male child was referred to the CHD clinic, National Research Centre, presenting with dysmorphic features and CHD. The patient was referred to the human cytogenetics department for cytogenetic analysis and for screening of subtelomere rearrangements and microdeletion loci, using MLPA, and all revealed normal results. CMA revealed an interstitial 2.27-Mb microdeletion in chromosome 2q, involving the entire ZEB2 gene and other genes. This study emphasizes the significance of CMA in the detection of microdeletions/microduplications and as a screening tool in cases presenting with CHD and extracardiac manifestations. MWS should be suspected in...
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Papers by Khaled Refaat