De novo germline PTEN mutation in a man with Lhermitte-Duclos disease which arose on the paternal chromosome and was transmitted to his child with polydactyly and Wormian bones

Abstract Background The lower Dipteran fungus fly, Sciara coprophila, has many unique biological features that challenge the rule of genome DNA constancy. For example, Sciara undergoes paternal chromosome elimination and maternal X chromosome nondisjunction during spermatogenesis, paternal X elimination during embryogenesis, intrachromosomal DNA amplification of DNA puff loci during larval development, and germline-limited chromosome elimination from all somatic cells. Paternal chromosome elimination in Sciara was the first observation of imprinting, though the mechanism remains a mystery. Here, we present the first draft genome sequence for Sciara coprophila to take a large step forward in addressing these features. Results We assembled the Sciara genome using PacBio, Nanopore, and Illumina sequencing. To find an optimal assembly using these datasets, we generated 44 short-read and 50 long-read assemblies. We ranked assemblies using 27 metrics assessing contiguity, gene content, and dataset concordance. The highest-ranking assemblies were scaffolded using BioNano optical maps. RNA-seq datasets from multiple life stages and both sexes facilitated genome annotation. A set of 66 metrics was used to select the first draft assembly for Sciara. Nearly half of the Sciara genome sequence was anchored into chromosomes, and all scaffolds were classified as X-linked or autosomal by coverage. Conclusions We determined that X-linked genes in Sciara males undergo dosage compensation. An entire bacterial genome from the Rickettsia genus, a group known to be endosymbionts in insects, was co-assembled with the Sciara genome, opening the possibility that Rickettsia may function in sex determination in Sciara. Finally, the signal level of the PacBio and Nanopore data support the presence of cytosine and adenine modifications in the Sciara genome, consistent with a possible role in imprinting.

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Muscle Hemangiomatosis Presenting as a Severe Feature in a Patient with the Pten Mutation: Expanding the Phenotype of Vascular Malformations in Bannayan-Riley-ruvalcaba Syndrome

Balkan Journal of Medical Genetics ◽

10.2478/v10034-012-0007-x ◽

2012 ◽

Vol 15 (1) ◽

pp. 45-50 ◽

Cited By ~ 1

Author(s):

Y Soysal ◽

T Acun ◽

C Lourenço ◽

W Marques ◽

M Yakıcıer

Keyword(s):

Dna Sequencing ◽

Medical Care ◽

Clinical Features ◽

Mutation Analysis ◽

De Novo ◽

Vascular Malformations ◽

Premature Termination Codon ◽

Vascular Anomalies ◽

Termination Codon ◽

Pten Mutation

Muscle Hemangiomatosis Presenting as a Severe Feature in a Patient with the Pten Mutation: Expanding the Phenotype of Vascular Malformations in Bannayan-Riley-ruvalcaba SyndromeBannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare autosomal, dominantly-inherited, hamartoma syndrome with distinct phenotypic features. Mutations in the PTEN gene have been identified in PTEN hamartoma tumor syndromes. Our aim was to determine the correlation of phenotype-genotype relationships in a BRRS case. We have evaluated a PTEN mutation in a patient with vascular anomalies and the phenotypic findings of BRRS. We described an 8-year-old girl with the clinical features of BRRS, specifically with vascular anomalies. The mutation in the PTEN gene was identified by DNA sequencing. In our patient, we defined a de novo nonsense R335X (c.1003 C>T) mutation in exon 8, which results in a premature termination codon. Due to vascular anomalies and hemangioma, the patient's left leg was amputated 1 year after the hemangioma diagnosis. Bannayan - Riley - Ruvalcaba syndrome patients with macrocephaly and vascular anomalies should be considered for PTEN mutation analysis and special medical care.

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New PTEN mutation identified in a patient with rare bilateral choroidal ganglioneuroma

10.21203/rs.3.rs-32912/v4 ◽

2020 ◽

Author(s):

Zhaoxin Jiang ◽

Ting Zhang ◽

Chonglin Chen ◽

Limei Sun ◽

Songshan Li ◽

...

Keyword(s):

Genetic Analysis ◽

De Novo ◽

Family Members ◽

Genetic Alterations ◽

Unrelated Control ◽

Pten Mutation ◽

Whole Exome ◽

The Family ◽

Multiple Abnormalities ◽

Human Genome Reference

Abstract Background: Choroidal ganglioneuroma is an extremely rare tumor, and there is little knowledge regarding its pathogenesis. We aimed to investigate the phenotypic and genetic alterations in one sporadic patient with a rare case of bilateral choroidal ganglioneuroma. Methods: A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited for the study. Comprehensive ophthalmic examinations were performed. Genomic DNA was extracted from the peripheral blood samples collected from the patient, his unaffected family members, and 200 unrelated control subjects from the same population. Whole exome sequencing was performed and raw reads were aligned to the human genome reference (hg19) using Burrows-Wheeler Aligner. DNA from all available family members was Sanger sequenced for segregation analysis. Results: Extensive bilateral retinal detachments were observed via optical coherence tomography. Diffuse thickening of choroid was identified with ultrasound B scan and magnetic resonance imaging. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was present in the affected individual, but not in any of the family members. Genetic analysis revealed that there was no mutation in neurofibromatosis-related genes in the family. Upon performing comprehensive systemic examinations, no obvious abnormalities in other organs were observed. Conclusions: A novel de novo PTEN mutation was identified in a patient with bilateral choroidal ganglioneuroma. Although PTEN mutations are known to induce multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm the association between choroidal ganglioneuroma and PTEN mutation.

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New mutation in PTEN identified in patient with rare bilateral choroidal ganglioneuroma

10.21203/rs.3.rs-32912/v2 ◽

2020 ◽

Author(s):

Zhaoxin Jiang ◽

Ting Zhang ◽

Chonglin Chen ◽

Limei Sun ◽

Songshan Li ◽

...

Keyword(s):

Genetic Analysis ◽

De Novo ◽

Family Members ◽

Genetic Alterations ◽

Unrelated Control ◽

Pten Mutation ◽

Whole Exome ◽

New Association ◽

Multiple Abnormalities ◽

Human Genome Reference

Abstract Background: Choroidal ganglioneuroma is an extremely rare tumor, with little known regarding its pathogenesis. The present study aimed to investigate the phenotype and genetic alterations in one sporadic patient with rare bilateral choroidal ganglioneuroma.Methods: A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited in this study. Comprehensive ophthalmic examinations were performed in the patient. Genomic DNA was extracted from peripheral blood collected from the patient, the patient's unaffected family members, and from 200 unrelated control subjects from the same population. Whole exome sequencing was carried out and raw reads were aligned to the human genome reference (hg19) using the Burrows Wheeler Aligner. All available family members were subjected to Sanger sequencing for segregation analysis.Results: Bilateral and extensive retinal detachments were observed in OCT. The diffuse thickening of choroid was identified in B scan and MRI. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was identified in the affected individual, but not in any of the unaffected family members. Genetic analysis showed that there was no mutant in neurofibromatosis-related genes. There were no obvious abnormalities in other organs in comprehensive systemic examinations. Conclusions: A novel de novo PTEN mutation was identified in a bilateral choroidal ganglioneuroma case. Although PTEN mutation has been considered to induces multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm this new association between choroidal ganglioneuroma and the PTEN mutation.

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A case report on Wolf-Hirschhorn syndrome

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20211092 ◽

2021 ◽

Vol 8 (4) ◽

pp. 764

Author(s):

Naveen Kumar ◽

Sapna Berry

Keyword(s):

Hearing Loss ◽

Genetic Disease ◽

De Novo ◽

Heart Defects ◽

Chromosome 4 ◽

Paternal Chromosome ◽

Genetic Condition ◽

Neurocognitive Development ◽

Characteristic Appearance ◽

Severe Intellectual Disability

Wolf-Hirschhorn syndrome is a genetic condition that affects many systems of the human body. It is caused by a deletion of the band 4p16.3 and this deletion may be sub microscopic. Individuals affected by the syndrome have a special phenotype: wide bridge of the nose, widely spaced eyes, micrognathia, microcephaly, growth retardation, cryptorchidism, heart defects, hearing loss and severe intellectual disability. A familial translocation is seen in 5-13% of the patients. Other patients have de novo deletions, usually on the paternal chromosome 4, or de novo translocations in 1.6%. Prenatal diagnosis is possible. We are hereby reporting a case of 9 months old infant who showed delayed physical and neurocognitive development and a characteristic appearance, which led to the diagnosis of this genetic disease.

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A New Case of Beckwith-Wiedemann Syndrome with an 11p15 Duplication of Paternal Origin [46,XY,-21,+der(21), t(11;21)(p15.2;q22.3)pat]

Acta geneticae medicae et gemellologiae twin research ◽

10.1017/s0001566000001392 ◽

1996 ◽

Vol 45 (1-2) ◽

pp. 245-250 ◽

Cited By ~ 8

Author(s):

M. Krajewska-Walasek ◽

A. Gutkowska ◽

M. Mospinek-Krasnopolska ◽

K. Chrzanowska

Keyword(s):

Dna Analysis ◽

De Novo ◽

Severe Mental Retardation ◽

Paternal Chromosome ◽

Balanced Translocation ◽

Paternal Origin ◽

Clinically Normal ◽

Paternal Grandmother ◽

Normal Father

AbstractWe present a new case of 11p15 duplication (trisomy 11p15) in a boy [46,XY,-21,+der(21), t(11;21)(p15.2;q22.3)] suffering from Beckwith-Wiedemann syndrome (BWS), whose phenotypically normal father carries a balanced translocation between chromosomes 11 and 21[46,XY, t(11;21)(p15.2;q22.3)]. The paternal grandmother has the same balanced translocation and is also clinically normal. BWS was suspected when the boy was 6 months old because of gigantism, macroglossia, visceromegaly, ear lobe creases and abdominal distention. Apart from the characteristic BWS phenotype, the boy has other features which are almost exclusively observed in 11p trisomy (high forehead with frontal upsweep of hair, wide central nose bridge, slightly beaked nose, chubby cheeks and severe mental retardation). So far, at least eight cases of 11p15 duplication have been described as patients with BWS. In six of these, the duplication was due to inheritance of a translocated or rearranged paternal chromosome. This was also the case in our patient. In the two other previously published cases, the 11p15 duplications were de novo, but in one of these, DNA analysis has subsequently shown that the duplication was of paternal origin. We discuss our observations in relation to the above-mentioned previous cases of 11p15 duplication and the possible role of genomic imprinting in the etiology of BWS.

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New mutation in PTEN identified in patient with rare bilateral choroidal ganglioneuroma

10.21203/rs.3.rs-32912/v1 ◽

2020 ◽

Author(s):

Zhaoxin Jiang ◽

Ting Zhang ◽

Chonglin Chen ◽

Limei Sun ◽

Songshan Li ◽

...

Keyword(s):

Genetic Analysis ◽

De Novo ◽

Family Members ◽

Genetic Alterations ◽

Unrelated Control ◽

Pten Mutation ◽

Whole Exome ◽

New Association ◽

Multiple Abnormalities ◽

Human Genome Reference

Abstract Background Choroidal ganglioneuroma is an extremely rare tumor, with little known regarding its pathogenesis. The present study aimed to investigate the phenotype and genetic alterations in one sporadic patient with rare bilateral choroidal ganglioneuroma. Methods A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited in this study. Comprehensive ophthalmic examinations were performed in the patient. Genomic DNA was extracted from peripheral blood collected from the patient, the patient's unaffected family members, and from 200 unrelated control subjects from the same population. Whole exome sequencing was carried out and raw reads were aligned to the human genome reference (hg19) using the Burrows Wheeler Aligner. All available family members were subjected to Sanger sequencing for segregation analysis. Results Bilateral and extensive retinal detachments were observed in OCT. The diffuse thickening of choroid was identified in B scan and MRI. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was identified in the affected individual, but not in any of the unaffected family members. Genetic analysis showed that there was no mutant in neurofibromatosis-related genes. There were no obvious abnormalities in other organs in comprehensive systemic examinations. Conclusions A novel de novo PTEN mutation was identified in a bilateral choroidal ganglioneuroma case. Although PTEN mutation has been considered to induces multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm this new association between choroidal ganglioneuroma and the PTEN mutation.

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Single-molecule sequencing of long DNA molecules allows high contiguity de novo genome assembly for the fungus fly, Sciara coprophila

10.1101/2020.02.24.963009 ◽

2020 ◽

Author(s):

John M. Urban ◽

Michael S. Foulk ◽

Jacob E. Bliss ◽

C. Michelle Coleman ◽

Nanyan Lu ◽

...

Keyword(s):

Genome Sequence ◽

Single Molecule ◽

De Novo ◽

Draft Genome ◽

Chromosome Elimination ◽

Future Research ◽

Paternal Chromosome ◽

Oxford Nanopore ◽

Dna Modifications ◽

Long Read

ABSTRACTThe lower Dipteran fungus fly, Sciara coprophila, has many unique biological features. For example, Sciara undergoes paternal chromosome elimination and maternal X chromosome nondisjunction during spermatogenesis, paternal X elimination during embryogenesis, intrachromosomal DNA amplification of DNA puff loci during larval development, and germline-limited chromosome elimination from all somatic cells. Paternal chromosome elimination in Sciara was the first observation of imprinting, though the mechanism remains a mystery. Here, we present the first draft genome sequence for Sciara coprophila to take a large step forward in aiding these studies. We approached assembling the Sciara genome using multiple sequencing technologies: PacBio, Oxford Nanopore MinION, and Illumina. To find an optimal assembly using these datasets, we generated 44 Illumina assemblies using 7 short-read assemblers and 50 long-read assemblies of PacBio and MinION sequence data using 6 long-read assemblers. We ranked assemblies using a battery of reference-free metrics, and scaffolded a subset of the highest-ranking assemblies using BioNano Genomics optical maps. RNA-seq datasets from multiple life stages and both sexes facilitated genome annotation. Moreover, we anchored nearly half of the Sciara genome sequence into chromosomes. Finally, we used the signal level of both the PacBio and Oxford Nanopore data to explore the presence or absence of DNA modifications in the Sciara genome since DNA modifications may play a role in imprinting in Sciara, as they do in mammals. These data serve as the foundation for future research by the growing community studying the unique features of this emerging model system.

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