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Wasim Ahmad - One of the best experts on this subject based on the ideXlab platform.
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Woodhouse-Sakati Syndrome in a family is associated with a homozygous start loss mutation in the DCAF17 gene.
Clinical and Experimental Dermatology, 2019Co-Authors: Khadim Shah, Sulman Basit, Farooq Ahmad, Khushnooda Ramzan, Wasim AhmadAbstract:BACKGROUND: Woodhouse-Sakati Syndrome (WSS) is a rare neuroendocrine and ectodermal disorder inherited in an autosomal recessive pattern. The Syndrome presents prominent clinical features, including alopecia, neuroendocrine defects, neurological findings and progressive hearing loss. The condition results from mutations in the DCAF17 gene. AIMS: To search for the underlying genetic defect in a Pakistani family with WSS phenotypes. METHODOLOGY: Whole exome sequencing was used to search for the disease-causing variant. RESULTS: Analysis of the exome data revealed a start loss sequence variant (c.1A>G, p.M1?) in DCAF17. CONCLUSION: This variant is predicted to abolish translation of the DCAF17 polypeptide. To our knowledge, this is the first start loss variant identified in the DCAF17.
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Exome sequencing revealed a novel biallelic deletion in the DCAF17 gene underlying Woodhouse Sakati Syndrome.
Clinical Genetics, 2016Co-Authors: Khadim Shah, Abdul Nasir, Wouter Steyaert, Paul Coucke, Wasim AhmadAbstract:Woodhouse Sakati Syndrome (WSS, MIM 241080) is a rare autosomal recessive genetic condition characterized by alopecia, hypogonadism, hearing impairment, diabetes mellitus, learning disabilities and extrapydamidal manifestations. Sequence variants in the gene DCAF17, encoding nucleolar substrate receptor, were identified as the underlying cause of inherited WSS. Considerable phenotypic heterogeneity exists in WSS with regard to severity, organs involvement and age of onset, both in inter-familial and intra-familial cases. In this study, the genetic characterization of a consanguineous pedigree showing mild features of WSS was performed, followed by structural analysis of truncated protein. Exome sequencing identified a novel single base deletion variant (c.270delA; K90Nfs8*) in third exon of the gene DCAF17 (RefSeq; NM_025000), resulting in a truncated protein. Structural analysis of truncated DCAF17 revealed absence of amino acid residues crucial for interaction with DDB1. Taken together, the data confirmed the single base pair deletion as the underlying cause of this second report of WSS from Pakistan. This signifies the vital yet unexplored role of DCAF17 both in development and maintenance of adult tissues homeostasis.
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A novel splice site mutation in gene C2orf37 underlying Woodhouse–Sakati Syndrome (WSS) in a consanguineous family of Pakistani origin
Gene, 2011Co-Authors: Rabia Habib, Sulman Basit, Saadullah Khan, Muhammad Nasim Khan, Wasim AhmadAbstract:Abstract Woodhouse–Sakati Syndrome (WSS) is a rare autosomal recessive multisystemic disorder that is marked by hypogonadism, alopecia, intellectual disability, deafness, diabetes mellitus and progressive extrapyramidal defects. Mutations in the gene C2orf37 are the cause of Woodhouse–Sakati Syndrome. In the present study, a four-generation consanguineous family with clinical manifestations of WSS was ascertained from a remote region of Pakistan. Linkage in the family was tested using microsatellite markers linked to several genes involved in producing WSS related phenotypes. Linkage in the family was established to the gene C2orf37, mapped on chromosome 2q22.3–2q35. DNA sequence analysis revealed a novel splice site mutation involving a homozygous G → A transition in the splice donor site of intron 3 (c.321 + 1 G > A) of C2orf37. This study presents a first report of Woodhouse–Sakati Syndrome identified in Pakistani population.
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A novel splice site mutation in gene C2orf37 underlying Woodhouse-Sakati Syndrome (WSS) in a consanguineous family of Pakistani origin.
Gene, 2011Co-Authors: Rabia Habib, Sulman Basit, Saadullah Khan, Muhammad Nasim Khan, Wasim AhmadAbstract:Woodhouse-Sakati Syndrome (WSS) is a rare autosomal recessive multisystemic disorder that is marked by hypogonadism, alopecia, intellectual disability, deafness, diabetes mellitus and progressive extrapyramidal defects. Mutations in the gene C2orf37 are the cause of Woodhouse-Sakati Syndrome. In the present study, a four-generation consanguineous family with clinical manifestations of WSS was ascertained from a remote region of Pakistan. Linkage in the family was tested using microsatellite markers linked to several genes involved in producing WSS related phenotypes. Linkage in the family was established to the gene C2orf37, mapped on chromosome 2q22.3-2q35. DNA sequence analysis revealed a novel splice site mutation involving a homozygous G→A transition in the splice donor site of intron 3 (c.321+1G>A) of C2orf37. This study presents a first report of Woodhouse-Sakati Syndrome identified in Pakistani population.
Ahmad Teebi - One of the best experts on this subject based on the ideXlab platform.
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phenotypic heterogeneity in woodhouse sakati Syndrome two new families with a mutation in the c2orf37 gene
American Journal of Medical Genetics Part A, 2011Co-Authors: Mariam Almureikhi, Seham Alameer, Christopher A Walsh, Jillian M Felie, Ahmad Teebi, Tawfeg Benomran, Muna AlsaffarAbstract:Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal Syndrome [also known as Woodhouse–Sakati Syndrome (WSS)] is a rare autosomal recessive neuroendocrine and ectodermal disorder. The Syndrome was first described by Woodhouse and Sakati in 1983, and 47 patients from 23 families have been reported so far. We report on an additional seven patients (four males and three females) from two highly consanguineous Arab families from Qatar, presenting with a milder phenotype of WSS. These patients show the spectrum of clinical features previously found in WSS, but lack evidence of diabetes mellitus and extrapyramidal symptoms. These two new families further illustrate the natural course and the interfamilial phenotypic variability of WSS that may lead to challenges in making the diagnosis. In addition, our study suggests that WSS may not be as infrequent in the Arab world as previously thought. © 2011 Wiley Periodicals, Inc.
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Phenotypic heterogeneity in Woodhouse-Sakati Syndrome: two new families with a mutation in the C2orf37 gene.
American journal of medical genetics. Part A, 2011Co-Authors: Tawfeg Ben-omran, Mariam Almureikhi, Seham Alameer, Muna Al-saffar, Christopher A Walsh, Jillian M Felie, Ahmad TeebiAbstract:Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal Syndrome [also known as Woodhouse-Sakati Syndrome (WSS)] is a rare autosomal recessive neuroendocrine and ectodermal disorder. The Syndrome was first described by Woodhouse and Sakati in 1983, and 47 patients from 23 families have been reported so far. We report on an additional seven patients (four males and three females) from two highly consanguineous Arab families from Qatar, presenting with a milder phenotype of WSS. These patients show the spectrum of clinical features previously found in WSS, but lack evidence of diabetes mellitus and extrapyramidal symptoms. These two new families further illustrate the natural course and the interfamilial phenotypic variability of WSS that may lead to challenges in making the diagnosis. In addition, our study suggests that WSS may not be as infrequent in the Arab world as previously thought.
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Phenotypic heterogeneity in Woodhouse–Sakati Syndrome: Two new families with a mutation in the C2orf37 gene
American Journal of Medical Genetics Part A, 2011Co-Authors: Tawfeg Ben-omran, Mariam Almureikhi, Seham Alameer, Muna Al-saffar, Christopher A Walsh, Jillian M Felie, Ahmad TeebiAbstract:Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal Syndrome [also known as Woodhouse–Sakati Syndrome (WSS)] is a rare autosomal recessive neuroendocrine and ectodermal disorder. The Syndrome was first described by Woodhouse and Sakati in 1983, and 47 patients from 23 families have been reported so far. We report on an additional seven patients (four males and three females) from two highly consanguineous Arab families from Qatar, presenting with a milder phenotype of WSS. These patients show the spectrum of clinical features previously found in WSS, but lack evidence of diabetes mellitus and extrapyramidal symptoms. These two new families further illustrate the natural course and the interfamilial phenotypic variability of WSS that may lead to challenges in making the diagnosis. In addition, our study suggests that WSS may not be as infrequent in the Arab world as previously thought. © 2011 Wiley Periodicals, Inc.
Rabia Habib - One of the best experts on this subject based on the ideXlab platform.
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Genetic Mapping of Genes Causing Human Hereditary Alopecias and Ectodermal Dysplasias
2020Co-Authors: Rabia HabibAbstract:Hereditary alopecias and ectodermal dysplasias are genetically heterogeneous groups of congenital disorders involving abnormalities in ectodermal appendages (hair, nail, teeth, sweat glands).These hereditary disorders may occur either as an isolated condition or associated with defects in other organ/organ systems.Over the past few years, investigations into molecular basis of these genetic disorders have yielded insights into the functional pathways and mechanisms involved in biology of skin appendages. The present study deals with clinical and molecular characterization of fifteen consanguineous families segregating disorders of hairs and ectodermal dysplasias. In addition, five candidate genes were screened in three other families exhibiting alopecia and mental retardation (APMR) Syndrome. Autosomal recessive form of isolated hypotrichosis was identified in six families (AF). Sequence analysis of Lipase H (LIPH) gene, mapped on chromosome 3q27, identified a novel splice-site mutation (c.629-1G>C) in family A, and two recurrent variants (c.659-660delTA [p.Ile220Argfs*25]; c.322T > C [p.Trp108Arg]) in three families (B-D).Four other families (G-J) demonstrated syndromic forms of hair loss disorders including juvenile macular dystrophy (HJMD), (APMR) and Woodhouse- Sakati Syndrome (WSS).Two of these families, showing different phenotypes, mapped on chromosome 2q22.3-q31.1. In one of the family (J), sequence analysis identified a novel splice site mutation (c.321+1G>A) in the gene C2orf37. Five other families, presented in the dissertation, exhibited different forms of ectodermal dysplasias including a novel type with hypotrichosis, nail dystrophy and reticulate pattern of hyperpigmentation in family N.SNP based genome wide analysis mapped the phenotype on chromosome 18p11.32-p11.31. However, screening 17 candidate genes, located within the linkage interval, failed to detect any potential sequence variant.In family O with pure hair and nail ectodermal dysplasia (PHNED), a novel duplication mutation (c.200-203dupGCCA [p.His68Glnfs*84]) was detected in the recently reported gene HOXC13, mapped on chromosome 12p11.1-q21.1. In a large family (R), segregating nail and bone deformity (brachydactyly type B1) in autosomal dominant fashion, screening the gene ROR2 revealed a previously known nonsense mutation (c.2278C>T [p.Q760*]). Overall, the knowledge derived from identification of different disease causing gene variants and locus enhances our understanding of genetic basis of these rare and diverse inherited skin disorders in Pakistani population and adds data to the growing mutation database for selected genetic disorders.These are the initial steps taken to unveil the molecular pathways involved in the pathophysiologies of the disorders and gives incentives for further studies into genotype-phenotype correlation, gene functional studies and for prognostic implications in pre-natal diagnosis and clinical management of the disease. The work presented in the dissertation contributed in publishing the following articles. 1. Habib R, Ansar M, Shahid M, Ali G, Ahmad W, Betz RC (2013). A Novel Locus for Ectodermal Dysplasia of Hair, Nail and Skin pigmentation anomalies Maps to Chromosome 18p11.32i?½€“11.31. (Submitted to Clinical Genetic). 2. Ali RH, Habib R, Ud-Din N, Khan MN, Ansar M, Ahmad W (2013). Novel mutations in the gene HOXC13 underlying pure hair and nail ectodermal dysplasia in consanguineous families. British Journal of Dermatology (In Press) (Co first author). 3. Habib R, Amin-Ud-Din M, Ahmad W (2013).A nonsense mutation in the gene ROR2 underlying autosomal dominant brachydactyly type B. Clinical Dysmorphology 22: 47-50. 4. Habib R, Basit S, Khan S, Khan MN, Ahmad W (2011).A novel splice site mutation in gene C2orf37 underlying Woodhouse-Sakati Syndrome (WSS) in a consanguineous family of Pakistani origin. Gene 490: 26-31. 5. Khan S, Habib R, Mir H, Umm-e-Kalsoom, Naz G, Ayub M, Shafique S, Yamin T, Ali N, Basit S, Wasif N, Kamran-ul-Hassan Naqvi S, Ali G, Wali A, Ansar M, Ahmad W (2011). Mutations in the LPAR6 and LIPH genes underlie autosomal recessive hypotrichosis/woolly hair in 17 consanguineous families from Pakistan. Clinical and Experimental Dermatology 36: 652-654.6. Kalsoom UE, Habib R, Khan B, Ali G, Ali N, Ansar M, Ahmad W (2010). Mutations in lipase H gene underlie autosomal recessive hypotrichosis in five Pakistani families. Acta Dermatological Venereology 90: 93-94.
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A novel splice site mutation in gene C2orf37 underlying Woodhouse–Sakati Syndrome (WSS) in a consanguineous family of Pakistani origin
Gene, 2011Co-Authors: Rabia Habib, Sulman Basit, Saadullah Khan, Muhammad Nasim Khan, Wasim AhmadAbstract:Abstract Woodhouse–Sakati Syndrome (WSS) is a rare autosomal recessive multisystemic disorder that is marked by hypogonadism, alopecia, intellectual disability, deafness, diabetes mellitus and progressive extrapyramidal defects. Mutations in the gene C2orf37 are the cause of Woodhouse–Sakati Syndrome. In the present study, a four-generation consanguineous family with clinical manifestations of WSS was ascertained from a remote region of Pakistan. Linkage in the family was tested using microsatellite markers linked to several genes involved in producing WSS related phenotypes. Linkage in the family was established to the gene C2orf37, mapped on chromosome 2q22.3–2q35. DNA sequence analysis revealed a novel splice site mutation involving a homozygous G → A transition in the splice donor site of intron 3 (c.321 + 1 G > A) of C2orf37. This study presents a first report of Woodhouse–Sakati Syndrome identified in Pakistani population.
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A novel splice site mutation in gene C2orf37 underlying Woodhouse-Sakati Syndrome (WSS) in a consanguineous family of Pakistani origin.
Gene, 2011Co-Authors: Rabia Habib, Sulman Basit, Saadullah Khan, Muhammad Nasim Khan, Wasim AhmadAbstract:Woodhouse-Sakati Syndrome (WSS) is a rare autosomal recessive multisystemic disorder that is marked by hypogonadism, alopecia, intellectual disability, deafness, diabetes mellitus and progressive extrapyramidal defects. Mutations in the gene C2orf37 are the cause of Woodhouse-Sakati Syndrome. In the present study, a four-generation consanguineous family with clinical manifestations of WSS was ascertained from a remote region of Pakistan. Linkage in the family was tested using microsatellite markers linked to several genes involved in producing WSS related phenotypes. Linkage in the family was established to the gene C2orf37, mapped on chromosome 2q22.3-2q35. DNA sequence analysis revealed a novel splice site mutation involving a homozygous G→A transition in the splice donor site of intron 3 (c.321+1G>A) of C2orf37. This study presents a first report of Woodhouse-Sakati Syndrome identified in Pakistani population.
Tawfeg Benomran - One of the best experts on this subject based on the ideXlab platform.
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phenotypic heterogeneity in woodhouse sakati Syndrome two new families with a mutation in the c2orf37 gene
American Journal of Medical Genetics Part A, 2011Co-Authors: Mariam Almureikhi, Seham Alameer, Christopher A Walsh, Jillian M Felie, Ahmad Teebi, Tawfeg Benomran, Muna AlsaffarAbstract:Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal Syndrome [also known as Woodhouse–Sakati Syndrome (WSS)] is a rare autosomal recessive neuroendocrine and ectodermal disorder. The Syndrome was first described by Woodhouse and Sakati in 1983, and 47 patients from 23 families have been reported so far. We report on an additional seven patients (four males and three females) from two highly consanguineous Arab families from Qatar, presenting with a milder phenotype of WSS. These patients show the spectrum of clinical features previously found in WSS, but lack evidence of diabetes mellitus and extrapyramidal symptoms. These two new families further illustrate the natural course and the interfamilial phenotypic variability of WSS that may lead to challenges in making the diagnosis. In addition, our study suggests that WSS may not be as infrequent in the Arab world as previously thought. © 2011 Wiley Periodicals, Inc.
Sulman Basit - One of the best experts on this subject based on the ideXlab platform.
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Woodhouse-Sakati Syndrome in a family is associated with a homozygous start loss mutation in the DCAF17 gene.
Clinical and Experimental Dermatology, 2019Co-Authors: Khadim Shah, Sulman Basit, Farooq Ahmad, Khushnooda Ramzan, Wasim AhmadAbstract:BACKGROUND: Woodhouse-Sakati Syndrome (WSS) is a rare neuroendocrine and ectodermal disorder inherited in an autosomal recessive pattern. The Syndrome presents prominent clinical features, including alopecia, neuroendocrine defects, neurological findings and progressive hearing loss. The condition results from mutations in the DCAF17 gene. AIMS: To search for the underlying genetic defect in a Pakistani family with WSS phenotypes. METHODOLOGY: Whole exome sequencing was used to search for the disease-causing variant. RESULTS: Analysis of the exome data revealed a start loss sequence variant (c.1A>G, p.M1?) in DCAF17. CONCLUSION: This variant is predicted to abolish translation of the DCAF17 polypeptide. To our knowledge, this is the first start loss variant identified in the DCAF17.
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A novel splice site mutation in gene C2orf37 underlying Woodhouse–Sakati Syndrome (WSS) in a consanguineous family of Pakistani origin
Gene, 2011Co-Authors: Rabia Habib, Sulman Basit, Saadullah Khan, Muhammad Nasim Khan, Wasim AhmadAbstract:Abstract Woodhouse–Sakati Syndrome (WSS) is a rare autosomal recessive multisystemic disorder that is marked by hypogonadism, alopecia, intellectual disability, deafness, diabetes mellitus and progressive extrapyramidal defects. Mutations in the gene C2orf37 are the cause of Woodhouse–Sakati Syndrome. In the present study, a four-generation consanguineous family with clinical manifestations of WSS was ascertained from a remote region of Pakistan. Linkage in the family was tested using microsatellite markers linked to several genes involved in producing WSS related phenotypes. Linkage in the family was established to the gene C2orf37, mapped on chromosome 2q22.3–2q35. DNA sequence analysis revealed a novel splice site mutation involving a homozygous G → A transition in the splice donor site of intron 3 (c.321 + 1 G > A) of C2orf37. This study presents a first report of Woodhouse–Sakati Syndrome identified in Pakistani population.
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A novel splice site mutation in gene C2orf37 underlying Woodhouse-Sakati Syndrome (WSS) in a consanguineous family of Pakistani origin.
Gene, 2011Co-Authors: Rabia Habib, Sulman Basit, Saadullah Khan, Muhammad Nasim Khan, Wasim AhmadAbstract:Woodhouse-Sakati Syndrome (WSS) is a rare autosomal recessive multisystemic disorder that is marked by hypogonadism, alopecia, intellectual disability, deafness, diabetes mellitus and progressive extrapyramidal defects. Mutations in the gene C2orf37 are the cause of Woodhouse-Sakati Syndrome. In the present study, a four-generation consanguineous family with clinical manifestations of WSS was ascertained from a remote region of Pakistan. Linkage in the family was tested using microsatellite markers linked to several genes involved in producing WSS related phenotypes. Linkage in the family was established to the gene C2orf37, mapped on chromosome 2q22.3-2q35. DNA sequence analysis revealed a novel splice site mutation involving a homozygous G→A transition in the splice donor site of intron 3 (c.321+1G>A) of C2orf37. This study presents a first report of Woodhouse-Sakati Syndrome identified in Pakistani population.