Megacystis Microcolon Intestinal Hypoperistalsis Syndrome: Case Reports and Discussion of the Literature

2015 ◽  
Vol 39 (2) ◽  
pp. 152-157 ◽  
Author(s):  
Joana De Sousa ◽  
Vipul Upadhyay ◽  
Peter Stone
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Case Reports ◽  
Dominant Inheritance ◽  
Genetic Studies ◽  
Intestinal Dysmotility ◽  
Autosomal Recessive Condition ◽  
Hypoperistalsis Syndrome ◽  
Autosomal Dominant Inheritance Pattern ◽  
Viable Treatment

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare intestinal dysmotility condition that also involves a dilated urinary bladder. It was believed to be an autosomal recessive condition, but genetic studies have suggested possibly an autosomal dominant inheritance pattern. Prenatal diagnosis can be challenging, but MRI and amniotic fluid/digestive fluid studies may be complementary investigations to improve diagnostic accuracy. Prognosis of MMIHS is generally poor and treatment is mostly supportive. To date, bowel transplantation remains the only viable treatment to restore bowel motility. Here we present two additional cases to contribute towards the scant literature on this condition.

Genomic features of lung cancer patients harboring germline mutations associated with hereditary cancer syndromes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20511-e20511
Author(s):  
Jian Sun ◽  
Weiran Wang ◽  
Danhua Wang ◽  
Hongling Yuan ◽  
Tonghui Ma
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Autosomal Recessive Inheritance ◽  
Germline Mutations ◽  
Autosomal Dominant Inheritance ◽  
Recessive Inheritance ◽  
Dominant Inheritance ◽  
Lung Cancer Patients

e20511 Background: Smoking and air pollution are the major causes of lung cancer; however, numerous studies have demonstrated that genetic factors also contribute to the development of lung cancer. Here, we reported an analysis of genomic features in 65 lung cancer patients with autosomal-dominant or autosomal-recessive inheritance of germline mutations. Methods: We retrospectively reviewed next-generation sequencing data of 26,904 lung cancer patients in a Chinese cohort. The germline mutation patterns, as well as the co-occurrence with somatic driver mutations were analyzed. Results: A total of 65 (0.24%) patients with heterozygous germline mutations associated with hereditary cancer syndromes were detected, including 27 (0.10%) patients with autosomal-dominant inheritance (BRCA1, BRCA2, RET and TP53) and 38 (0.14%) patients with autosomal-recessive inheritance (ATM, BLM, FANCA, FANCG, MUTYH, NBN, RECQL4 and WRN). Comparing to patients with autosomal-dominant inheritance (Age 56±17.8), patients with autosomal-recessive inheritance (Age 65±11.7, P = 0.009) were older, and there is no gender difference. Additionally, 66.7% (18/27) of patients with autosomal-dominant inheritance were identified co-mutated actionable variations, such as 12 patients harboring mutations in exon 18–21 of EGFR, 2 patients harboring ERBB2 exon 20 insertions, 3 patients harboring mutations in exon 2 of KRAS and 1 patient harboring EML4-ALK fusion. The coexistence of germline autosomal-dominant mutations and somatic driver mutations indicated that germline mutations have weak impact on lung cancer. Simultaneously, 52.6% (20/38) of patients with autosomal-recessive inheritance were identified co-mutated actionable variations, such as 15 EGFR+ patients, 2 ERBB2+ patients and 3 KRAS+ patients. And there was no significant difference in population frequency of co-mutated actionable variations between the two groups. Conclusions: In summary, studies on germline mutations of lung cancer patients may help to elucidate the etiology and mechanism of lung cancer, and may help for early detection and diagnosis, targeted therapy and improved prevention strategies.

scholarly journals Genetic hearing loss: a study of 228 Brazilian patients

2000 ◽  
Vol 23 (1) ◽  
pp. 25-27 ◽  
Author(s):  
Silvia Bragagnolo Longhitano ◽  
Décio Brunoni
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Autosomal Recessive Inheritance ◽  
Recessive Inheritance ◽  
Dominant Inheritance ◽  
Genetic Etiology ◽  
Parental Consanguinity ◽  
Genetic Hearing Loss ◽  
Associated Abnormalities

We studied 228 patients, with suspected or confirmed genetic hearing loss, in order to determine the clinical and genetic diagnoses and etiology of each case. Deafness with no associated abnormalities was found in 146 patients (64%) belonging to 112 families. Syndromic deafness was diagnosed in 82 patients (36%) belonging to 76 families. The genetic etiology was as follows: autosomal recessive inheritance in 40.8% of syndromics and non-syndromics, autosomal dominant inheritance in 13.2% and X-linked recessive in 1.3%. In 44.7% of the cases, the etiology of the hearing loss could not be determined. Monogenic causes are the most possible etiology in the latter cases. Parental consanguinity was found in 22.4% of the cases, and deafness was bilateral, profound and neurosensorial in 47.4% of the patients. An early onset of hearing loss (< 2 years of age) occurred in 46.5% of the cases. These results are similar to previous literature reports.

scholarly journals Insight into the autosomal-dominant inheritance pattern of SOD1-associated ALS from native mass spectrometry

2020 ◽  
Author(s):  
Jelena Cveticanin ◽  
Tridib Mondal ◽  
Elizabeth M. Meiering ◽  
Michal Sharon ◽  
Amnon Horovitz
Keyword(s):  
Mass Spectrometry ◽  
Autosomal Dominant ◽  
Native Mass Spectrometry ◽  
Autosomal Dominant Inheritance ◽  
Coupling Constant ◽  
Inheritance Pattern ◽  
Wild Type ◽  
Dominant Inheritance ◽  
Mutant Sod1 ◽  
Autosomal Dominant Inheritance Pattern

AbstractAbout 20% of all familial amyotrophic lateral sclerosis (ALS) cases are associated with mutations in superoxide dismutase (SOD1), a homodimeric protein. The disease has an autosomal-dominant inheritance pattern. It is, therefore, important to determine whether wild-type and mutant SOD1 subunits self-associate randomly or preferentially. A measure for the extent of bias in subunit association is the coupling constant determined in a double-mutant cycle type analysis. Here, cell lysates containing co-expressed wild-type and mutant SOD1 subunits were analyzed by native mass spectrometry to determine these coupling constants. Strikingly, we find a linear positive correlation between the coupling constant and the duration of the disease. Our results indicate that inter-subunit communication and a preference for heterodimerization greatly increase the disease severity.

scholarly journals Congenital Aspirin-like Defect As a Result of Autosomal Recessive Variants in PTGS1

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1156-1156
Author(s):  
Suthesh Sivapalaratnam ◽  
Hayman Melissa ◽  
Claire Lentaigne ◽  
Melissa Chan ◽  
Marilena Crescente ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Autosomal Recessive Inheritance ◽  
Recessive Inheritance ◽  
Dominant Inheritance ◽  
Platelet Function Disorders ◽  
First Time

Abstract Inherited defects of platelet function disorders are rare and difficult to diagnose due to lack of standardized platelet tests. An aspirin-like platelet defect is characterised by reduced thromboxane A2 (TXA2) signalling due to a defect in the arachidonic acid (AA) pathway in platelets. Patients with aspirin-like defect present with mild to moderate bleeding symptoms and impaired platelet aggregation responses to AA and ADP. This is similar to the irreversible effect of aspirin on platelets, which is mediated through inhibition of prostaglandin H synthase-1 also known as cyclooxygenase-1 (PTGS1/COX1). We for the first time report platelet function disorders due to autosomal recessive inheritance of variants in PTGS1. In a total of 3563 cases with bleeding disorders, comprising 1169 whole genome sequenced probands of the BRIDGE-BPD study and 2394 panel sequenced index cases of the ThromboGenomics cohort, we identified 15 unrelated cases of each cohort with an aspirin-like platelet function defect. Two of these cases had rare a variants in PTGS1, the gene encoding COX-1, which catalyses the conversion of arachidonic acid to prostaglandin H2. The first case presented with epistaxis and peri-operative bleeding. She had reduced platelet aggregation responses to arachidonic acid, ADP, collagen and epinephrine. Incubation of control blood with collagen resulted in enhanced levels of thromboxane B2, PGD2, PGE2, 11-HETE and 15-HETE which was absent in the index case.We identified a homozygous missense variant in PTGS1, p.Trp322Ser with a Combined Annotation Dependant Depletion Score (CADD) of 31.0. This variant was absent from GnomAD. The variant co-segregated in an autosomal recessive inheritance mode, with aspirin-like defect phenotype in the seven family members who were investigated. PTGS1 was not expressed on the platelets by western blot. Immunophenotyping demonstrated absence on the platelet surface but presence on neutrophils. The second case of the presented with menorrhagia, nosebleeds, easy bleeding and bruising. She had reduced aggregation responses to arachidonic acid, ADP, collagen and epinephrine. We identified two variants in cis: a splice-donor variant (g. 125133553 T>A), CADD 24.3; and an upstream non-coding variant (g. 125132069 C>G), CADD 16.63. The frequency of these variants were respectively; 1.7 x 10-5 and 8 x 10-3 in GnomAD. Platelet RNA and protein expression studies in the propositus revealed alternative splicing with the generation of a smaller protein due the splice variant. In contrast, the non coding variant had no effect on promoter or enhancer activity and therefore, is likely benign. In this case, the mode of inheritance is autosomal dominant with a dominant negative effect, which has been reported previously. For the other 13 cases of the Bridge-BPD study we also interrogated the non-coding space and interactors in the arachidonic acid pathway, none of which had genetic variants explaining the phenotype. For the 15 ThromboGenomics cohort cases because they were sequenced on targeted platform similar investigations could not take place. These cases could have a non inherited cause for the platelet defect or it is also permissible that variation in a hitherto undefined pathways unique to individual cases might be causal. In conclusion, we for the first time report autosomal recessive inheritance of variants in PTGS1 as cause for a rare inherited bleeding disorder. The effect of the mutation are selective loss of expression of PTGS1 within platelets and decreased enzyme function. Two previous reports demonstrated autosomal dominant inheritance. The first demonstrated autosomal dominant inheritance of variants in PTGS1 as modifier in a well characterized family with haemophilia A and platelet function disorder (Nance et al JTH 2016). The second reported rare heterozygous variants in PTGS1 in two cases with a bleeding tendency which was not further specified in the report (Bastida et al Haematologica 2018). Disclosures Laffan: Pfizer: Honoraria; Roche: Consultancy, Speakers Bureau.

scholarly journals Bilateral Optic Disc Pit with Maculopathy Case Report

2019 ◽  
Vol 75 (2) ◽  
pp. 86-90
Author(s):  
Veronika Radošová ◽  
Inka Krejčířová ◽  
Rudolf Autrata ◽  
Barbora Žajdlíková
Keyword(s):  
Optic Nerve ◽  
Optic Disc ◽  
Autosomal Dominant ◽  
Surgical Intervention ◽  
Asymptomatic Patient ◽  
Optic Disc Pit ◽  
Dominant Inheritance ◽  
Pars Plana ◽  
Therapeutic Possibilities ◽  
Autosomal Dominant Inheritance Pattern

An optic disc pit is a rare congenital anomaly of the optic nerve disc. It occurs rarely, and in case of its bilateral occurance, it can be caused by an autosomal dominant inheritance pattern. Ophthalmoscopically, the disc pit appears as an ovoid depression of the optic nerve disc. When identified unilaterally, the optic nerve disc is usually larger than the disc of the other healthy eye. Optic disc pits can be located anywhere in optic disc. Moreover, when located in the temporal margin, they can be accompanied by a maculopathy. The latest therapeutic possibilities include the retinal laser photocoagulation and pars plana vitrectomy, however the prognosis quoad visum neverthelles remains poor. This report deals with bilateral occurance of the optic disc pit in case of 9-year-old asymptomatic patient. The patient had been transferred to our ophthalmology department with suspected retinal detachment. Following the examination, the optic disc pit was diagnosed. The patient remains subject to further observation, however, owing to his current satisfactory vision without the need for a surgical intervention.

Congenital Stationary Night Blindness: Pathophysiology, Signs, Diagnosis, and Treatment

2021 ◽  
pp. 155-158
Keyword(s):  
Molecular Genetics ◽  
Night Blindness ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Common Type ◽  
Diagnosis And Treatment ◽  
Recessive Trait ◽  
Congenital Stationary Night Blindness ◽  
Dominant Inheritance ◽  
Retinal Disorder

Congenital stationary night blindness (CSNB) is a nonprogressive inherited retinal disorder characterized by lifelong night blindness. The Schubert-Bornschein type is the most common type of CSNB. The disease is most commonly inherited as an X-linked recessive trait, but can also have an autosomal recessive and rarely autosomal dominant inheritance. Clinical, electrophysiological, and molecular genetics about CSNB are reviewed in this paper.

PERIODIC PARALYSIS

2021 ◽  
Vol 19 (4) ◽  
pp. 457-461
Author(s):  
Е. V. Onegin ◽  
◽  
O. V. Mantsevich ◽  
Keyword(s):  
Autosomal Dominant ◽  
Case Reports ◽  
Treatment Options ◽  
Neuromuscular Disorder ◽  
Periodic Paralysis ◽  
Dominant Inheritance ◽  
Patient Case ◽  
Treatment Interventions ◽  
Sodium Calcium ◽  
Low Prevalence

Periodic paralysis (paroxysmal myoplegia) is a rare neuromuscular disorder caused by mutations in the sodium, calcium, and potassium channel genes of skeletal muscle. Common features of primary periodic paralysis are autosomal dominant inheritance, changes in serum potassium levels as a result of a defect in ion channels, and the onset of the disease in the first or second decade of life. Clinically, PP is manifested by episodic attacks of muscle weakness that occur at irregular intervals, attacks are often associated with food or rest after exercise, sometimes accompanied by myotonia. Periodic paralysis is rare in the general population and, as a result, prospective clinical trials of treatment interventions are limited. Due to the low prevalence of primary PCBs and limited treatment options, few prospective studies are available to develop treatment recommendations based on anecdotal evidence and patient case reports. Treatment options include provocation prevention, potassium and carbonic anhydrase inhibitors.

Pattern Dystrophies

2021 ◽  
pp. 208-212
Keyword(s):  
Visual Acuity ◽  
Older Patients ◽  
Autosomal Dominant ◽  
Specific Treatment ◽  
Dominant Inheritance ◽  
Choroidal Neovascular Membrane ◽  
Good Visual Acuity ◽  
Retinal Atrophy ◽  
Pigment Distribution ◽  
Autosomal Dominant Inheritance Pattern

Pattern dystrophies have been known since 1950 which have autosomal dominant inheritance pattern. Pattern dystrophies have been classified based on the pattern of the pigment distribution. Despite significant retinal changes, good visual acuity is often maintained. However, complications such as choroidal neovascular membrane and retinal atrophy may develop in older patients and can significantly decrease visual acuity. There is no specific treatment, but when complications arise, treatment should be done by reason.

Familial achalasia with an autosomal dominant pattern of inherence: Report of a Vietnamese family

MedPharmRes ◽  
2019 ◽  
Vol 3 (2) ◽  
pp. 25-28
Author(s):  
Trong Duc Quach ◽  
Yuji Urabe ◽  
Toru Hiyama
Keyword(s):  
Genetic Predisposition ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Case Reports ◽  
Autosomal Dominant Pattern ◽  
Three Generations ◽  
Dominant Pattern ◽  
Autosomal Recessive Pattern

Current pathophysiologic knowledge of achalasia suggests the important involvement of genetic predisposition. However, familial achalasia is very rare and most of the case reports in literature have shown an autosomal recessive pattern of inherence. We hereby report a case of familial achalasia with autosomal dominant pattern of inherence affecting ten members in three generations of a Vietnamese family.

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