The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Fowzan S Alkuraya - One of the best experts on this subject based on the ideXlab platform.
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Confirming the Recessive Inheritance of PERP‐related erythrokeratoderma
Clinical genetics, 2020Co-Authors: Nisha Patel, Eman Alobeid, Rana Helaby, Firdous Abdulwahab, Hanan E Shamseldin, Tarfa Alshidi, Salim Alkeraye, Fowzan S AlkurayaAbstract:Erythrokeratoderma (EK) is heterogeneous clinical entity characterized by excessive scaling with resulting erythrokeratotic plaques. Several genes have been linked to EK and they encode a number of proteins that are important for the integrity of the keratinocyte layer of the epidermis. PERP is a transcription factor that is activated by both p53 and p63. However, its deficiency in a mouse model appears to only recapitulate p63-mediated role in skin development and organization. We report an extended multiplex consanguineous family in which an EK phenotype with a striking similarity to that observed in Perp-/- mice, is mapped to an autozygous region on chromosome 6 that spans PERP. Whole-exome sequencing revealed a novel variant in PERP that fully segregated with the phenotype. Functional analysis of patient- and control-derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that Recessive Inheritance is also possible. Our results, therefore, support the establishment of an autosomal Recessive PERP-related EK phenotype in humans.
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confirming the Recessive Inheritance of perp related erythrokeratoderma
Clinical Genetics, 2020Co-Authors: Nisha Patel, Eman Alobeid, Rana Helaby, Firdous Abdulwahab, Hanan E Shamseldin, Tarfa Alshidi, Salim Alkeraye, Fowzan S AlkurayaAbstract:: Erythrokeratoderma (EK) is heterogeneous clinical entity characterized by excessive scaling with resulting erythrokeratotic plaques. Several genes have been linked to EK and they encode a number of proteins that are important for the integrity of the keratinocyte layer of the epidermis. PERP is a transcription factor that is activated by both p53 and p63. However, its deficiency in a mouse model appears to only recapitulate p63-mediated role in skin development and organization. We report an extended multiplex consanguineous family in which an EK phenotype with a striking similarity to that observed in Perp-/- mice, is mapped to an autozygous region on chromosome 6 that spans PERP. Whole-exome sequencing revealed a novel variant in PERP that fully segregated with the phenotype. Functional analysis of patient- and control-derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that Recessive Inheritance is also possible. Our results, therefore, support the establishment of an autosomal Recessive PERP-related EK phenotype in humans. This article is protected by copyright. All rights reserved.
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Gonadal mosaicism as a rare cause of autosomal Recessive Inheritance
Clinical genetics, 2013Co-Authors: Shamsa Anazi, Essam Al-sabban, Fowzan S AlkurayaAbstract:Autosomal Recessive diseases are typically caused by the biparental Inheritance of familial mutant alleles. Unusual mechanisms by which the Recessiveness of a mutant allele is unmasked include uniparental isodisomy and the occurrence of a de novo chromosomal rearrangement that disrupts the other allele. Gonadal mosaicism is a condition in which a postfertilization mutation is confined to the gamete precursors and is not detected in somatic tissues. Gonadal mosaicism is known to give the impression of autosomal Recessive Inheritance when recurrence of an autosomal-dominant condition among offspring of phenotypically normal parents is observed. Here, we report an extremely rare event in which maternal gonadal mosaicism for a Recessive mutation in COL4A4 caused the recurrence of Alport syndrome within a consanguineous family. Such rare occurrence should be taken into account when analyzing pedigrees both for clinical and research purposes.
L F Telles - One of the best experts on this subject based on the ideXlab platform.
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Short stature, brachydactyly, and Peters' anomaly (Peters'-plus syndrome): confirmation of autosomal Recessive Inheritance.
Journal of medical genetics, 1991Co-Authors: J C De Almeida, J C Llerena Júnior, J G Barbosa Neto, Ramos Pontes, S Middleton, L F TellesAbstract:Two sibs with a phenotype characterised by short stature, brachydactyly, and ocular anomalies (Peters' anomaly) are reported (Peters'-plus syndrome). The consanguinity is in agreement with the proposed autosomal Recessive Inheritance.
Paola Grammatico - One of the best experts on this subject based on the ideXlab platform.
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Elsahy-Waters syndrome: Evidence for autosomal Recessive Inheritance.
American journal of medical genetics. Part A, 2010Co-Authors: Marco Castori, Piero Cascone, Michele Valiante, Luigi Laino, Giorgio Iannetti, Raoul C M Hennekam, Paola GrammaticoAbstract:Elsahy-Waters or branchioskeletogenital syndrome is a rare MCA/MR syndrome characterized by moderate mental retardation, hypospadias and characteristic craniofacial morphology, which includes brachycephaly, facial asymmetry, exotropia, hypertelorism/telechantus, broad nose, concave nasal ridge, underdeveloped midface, prognathism, and radicular dentin dysplasia. Here we report on a 44-year-old woman and her 45-year-old brother, born to consanguineous parents, who show a striking resemblance to the earlier described patients. The hitherto reported patients were male and in one pedigree parents were consanguineous. The present report of an affected woman and her brother, born to consanguineous parents, supports autosomal Recessive Inheritance of this condition. We provide a short review of all previously reported patients with Elsahy-Waters syndrome and related entities.
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Elsahy–Waters syndrome: Evidence for autosomal Recessive Inheritance†
American Journal of Medical Genetics Part A, 2010Co-Authors: Marco Castori, Piero Cascone, Michele Valiante, Luigi Laino, Giorgio Iannetti, Raoul C M Hennekam, Paola GrammaticoAbstract:Elsahy-Waters or branchioskeletogenital syndrome is a rare MCA/MR syndrome characterized by moderate mental retardation, hypospadias and characteristic craniofacial morphology, which includes brachycephaly, facial asymmetry, exotropia, hypertelorism/telechantus, broad nose, concave nasal ridge, underdeveloped midface, prognathism, and radicular dentin dysplasia. Here we report on a 44-year-old woman and her 45-year-old brother, born to consanguineous parents, who show a striking resemblance to the earlier described patients. The hitherto reported patients were male and in one pedigree parents were consanguineous. The present report of an affected woman and her brother, born to consanguineous parents, supports autosomal Recessive Inheritance of this condition. We provide a short review of all previously reported patients with Elsahy-Waters syndrome and related entities.
Nada Al Tassan - One of the best experts on this subject based on the ideXlab platform.
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germline mosaicism for kif21a mutation p r954l mimicking Recessive Inheritance for congenital fibrosis of the extraocular muscles
Ophthalmology, 2010Co-Authors: Arif O. Khan, Dania S. Khalil, Latifa Al Sharif, Faisal E Alghadhfan, Nada Al TassanAbstract:Objective To document the genotype for familial congenital fibrosis of the extraocular muscles (CFEOM) with apparent autosomal Recessive Inheritance. Design Interventional family study. Participants Two affected siblings, 3 asymptomatic siblings, and their 2 asymptomatic parents. Methods Ophthalmologic examination and candidate gene analysis ( KIF21A and PHOX2A from venous blood samples) of the 2 affected siblings and their parents; confirmatory testing for 3 available asymptomatic siblings. Main Outcome Measures Significant clinical observations and results of gene testing. Results The 2 affected siblings had large-angle exotropia, moderate bilateral hypotropia, moderate bilateral ptosis, sluggish pupils, and almost complete ophthalmoloplegia with some abnormal synkinesis. The asymptomatic parents were not related and had unremarkable ophthalmic examinations. Four other siblings were normal by history; 3 underwent venous blood sampling for confirmatory testing. Candidate gene testing of PHOX2A , the gene for Recessive CFEOM (CFEOM2), did not reveal mutation in the 2 patients or their parents. Sequencing of KIF21A , the gene for dominant CFEOM (CFEOM1), revealed heterozygous p.R954L in both affected individuals but in not in their parents or 3 asymptomatic siblings, consistent with parental germline mosaicism. Haplotype analysis suggested paternal Inheritance but was not conclusive. Conclusions Parental germline mosaicism can mimic Recessive Inheritance in CFEOM and likely is underrecognized. Ophthalmologists should be aware of this phenomenon when counseling parents of children with apparent Recessive (or de novo) hereditary eye disease. Unlike other reported KIF21A mutations that cause CFEOM1, the p.R954L variant seems to be associated with abnormal pupils. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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germline mosaicism for kif21a mutation p r954l mimicking Recessive Inheritance for congenital fibrosis of the extraocular muscles
Ophthalmology, 2010Co-Authors: Arif O. Khan, Dania S. Khalil, Latifa Al Sharif, Faisal E Alghadhfan, Nada Al TassanAbstract:Objective To document the genotype for familial congenital fibrosis of the extraocular muscles (CFEOM) with apparent autosomal Recessive Inheritance. Design Interventional family study. Participants Two affected siblings, 3 asymptomatic siblings, and their 2 asymptomatic parents. Methods Ophthalmologic examination and candidate gene analysis ( KIF21A and PHOX2A from venous blood samples) of the 2 affected siblings and their parents; confirmatory testing for 3 available asymptomatic siblings. Main Outcome Measures Significant clinical observations and results of gene testing. Results The 2 affected siblings had large-angle exotropia, moderate bilateral hypotropia, moderate bilateral ptosis, sluggish pupils, and almost complete ophthalmoloplegia with some abnormal synkinesis. The asymptomatic parents were not related and had unremarkable ophthalmic examinations. Four other siblings were normal by history; 3 underwent venous blood sampling for confirmatory testing. Candidate gene testing of PHOX2A , the gene for Recessive CFEOM (CFEOM2), did not reveal mutation in the 2 patients or their parents. Sequencing of KIF21A , the gene for dominant CFEOM (CFEOM1), revealed heterozygous p.R954L in both affected individuals but in not in their parents or 3 asymptomatic siblings, consistent with parental germline mosaicism. Haplotype analysis suggested paternal Inheritance but was not conclusive. Conclusions Parental germline mosaicism can mimic Recessive Inheritance in CFEOM and likely is underrecognized. Ophthalmologists should be aware of this phenomenon when counseling parents of children with apparent Recessive (or de novo) hereditary eye disease. Unlike other reported KIF21A mutations that cause CFEOM1, the p.R954L variant seems to be associated with abnormal pupils. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.
J C De Almeida - One of the best experts on this subject based on the ideXlab platform.
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Short stature, brachydactyly, and Peters' anomaly (Peters'-plus syndrome): confirmation of autosomal Recessive Inheritance.
Journal of medical genetics, 1991Co-Authors: J C De Almeida, J C Llerena Júnior, J G Barbosa Neto, Ramos Pontes, S Middleton, L F TellesAbstract:Two sibs with a phenotype characterised by short stature, brachydactyly, and ocular anomalies (Peters' anomaly) are reported (Peters'-plus syndrome). The consanguinity is in agreement with the proposed autosomal Recessive Inheritance.
