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31.
Doris Škorić‐Milosavljević Fleur V. Y. Tjong Julien Barc Ad P. C. M. Backx Sally‐Ann B. Clur Karin van Spaendonck‐Zwarts Roelof‐Jan Oostra Najim Lahrouchi Leander Beekman Regina Bökenkamp Daniela Q. C. M. Barge‐Schaapveld Barbara J. Mulder Elisabeth M. Lodder Connie R. Bezzina Alex V. Postma 《American journal of medical genetics. Part A》2019,179(9):1836-1845
The first human mutations in GATA6 were described in a cohort of patients with persistent truncus arteriosus, and the phenotypic spectrum has expanded since then. This study underscores the broad phenotypic spectrum by presenting two patients with de novo GATA6 mutations, both exhibiting complex cardiac defects, pancreatic, and other abnormalities. Furthermore, we provided a detailed overview of all published human genetic variation in/near GATA6 published to date and the associated phenotypes (n = 78). We conclude that the most common phenotypes associated with a mutation in GATA6 were structural cardiac and pancreatic abnormalities, with a penetrance of 87 and 60%, respectively. Other common malformations were gallbladder agenesis, congenital diaphragmatic hernia, and neurocognitive abnormalities, mostly developmental delay. Fifty‐eight percent of the mutations were de novo, and these patients more often had an anomaly of intracardiac connections, an anomaly of the great arteries, and hypothyroidism, compared with those with inherited mutations. Functional studies mostly support loss‐of‐function as the pathophysiological mechanism. In conclusion, GATA6 mutations give a wide range of phenotypic defects, most frequently malformations of the heart and pancreas. This highlights the importance of detailed clinical evaluation of identified carriers to evaluate their full phenotypic spectrum. 相似文献
32.
Daphné Lehalle Roberto Colombo Michael O'Grady Bénédicte Héron Nada Houcinat Paul Kuentz Sebastien Moutton Arthur Sorlin Julien Thevenon Julian Delanne Sebastien Gay Caroline Racine Aurore Garde Frédéric Tran Mau‐Them Christophe Philippe Antonio Vitobello Sophie Nambot Frédéric Huet Yannis Duffourd François Feillet Christel Thauvin‐Robinet Sandrine Marlin Laurence Faivre 《American journal of medical genetics. Part A》2019,179(9):1756-1763
Alpha‐mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi‐systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha‐mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha‐mannosidase in leucocytes and screening for abnormal urinary excretion of mannose‐rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDER) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3–23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two‐sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management. 相似文献
33.
de Grave DD Biegstraaten M Smeets JB Brenner E 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2005,163(1):58-64
It is not evident how the small effects of the flankers of the Ebbinghaus figure on peak grip aperture (PGA) should be interpreted. One interpretation is that the flankers influence the estimated size, which in turn influences the grasp. If this interpretation is correct, then only the size-dependent aspects of the grasping movement should depend on the spatial positions of the flankers. An alternative interpretation is that the effect on grip aperture is caused by a change in judgement of the required precision, in which case various aspects of the grasping movement could be influenced by the size and position of the flankers. We presented subjects with a display consisting of a central disk surrounded by four large or small flankers. The array of circular flankers could be rotated by 45°. There were two tasks: to reproduce the perceived size of the central disk, and to grasp the central disk. As in other studies, the reproduced size and the PGA were both influenced by the size of the flankers. The effect on reproduced size settings was independent of the flankers spatial position. Nevertheless, the flankers position did influence the final grip aperture and the grip orientation at PGA and at movement offset. Because the flankers changed more than only the PGA, we conclude that the effect of the flankers on prehension cannot only be because of misjudgement of the size of the central disk. 相似文献
34.
Brice Poreau Francis Ramond Radu Harbuz Véronique Satre Claire Barro Claire Vettier Véronique Adouard Julien Thevenon Pierre‐Simon Jouk Charles Coutton Klaus Dieterich 《American journal of medical genetics. Part A》2019,179(4):650-654
The AMME syndrome defined as the combination of Alport syndrome, intellectual disability, midface hypoplasia, and elliptocytosis (AMME) is known to be a contiguous gene syndrome associated with microdeletions in the region Xq22.3q23. Recently, using exome sequencing, missense pathogenic variants in AMMECR1 have been associated with intellectual disability, midface hypoplasia, and elliptocytosis. In these cases, AMMECR1 gene appears to be responsible for most of the clinical features of the AMME syndrome except for Alport syndrome. In this article, we present two unrelated male patients with short stature, mild intellectual disability or neurodevelopmental delay, sensorineural hearing loss, and elliptocytosis harboring small microdeletions identified by array‐CGH involving TMEM164 and AMMECR1 genes and SNORD96B small nucleolar RNA for one patient, inherited from their mothers. These original cases further confirm that most specific AMME features are ascribed to AMMECR1 haploinsufficiency. These cases reporting the smallest microdeletions encompassing AMMECR1 gene provide new evidence for involvement of AMMECR1 in the AMME phenotype and permit to discuss a phenotype related to AMMECR1 haploinsufficiency: developmental delay/intellectual deficiency, midface hypoplasia, midline defect, deafness, and short stature. 相似文献
35.
36.
Igarashi S; Takiyama Y; Cancel G; Rogaeva EA; Sasaki H; Wakisaka A; Zhou YX; Takano H; Endo K; Sanpei K; Oyake M; Tanaka H; Stevanin G; Abbas N; Durr A; Rogaev EI; Sherrington R; Tsuda T; Ikeda M; Cassa E; Nishizawa M; Benomar A; Julien J; Weissenbach J; Tsuji S 《Human molecular genetics》1996,5(7):923-932
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative
disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at
14q32.1. To identify elements affecting the intergenerational instability
of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the
3' end of the CAG repeat affects intergenerational instability of the CAG
repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n- GGG] haplotypes were
found to result in significantly greater instability of the CAG repeat
compared to the [expanded (CAG)n- CGG]/[normal (CAG)n-CGG] or [expanded
(CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic
regression analysis revealed that the relative risk for a large
intergenerational change in the number of CAG repeat units (< -2 or >
2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal
transmission than in that of maternal transmission and 7.4-fold (95% CI:
2.4-23.3) higher in the case of transmission from a parent with the
[expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of
transmission from a parent with the [expanded (CAG)n-CGG]/[normal
(CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The
combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal
(CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase
in the relative risk compared with that of maternal transmission and the
[expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal
(CAG)n-GGG] haplotypes. The results suggest that an inter- allelic
interaction is involved in the intergenerational instability of the
expanded CAG repeat.
相似文献
37.
Loubinoux J Rio B Mihaila L Foïs E Le Fleche A Grimont PA Marie JP Bouvet A 《Journal of clinical microbiology》2005,43(7):3564-3566
A yellow-pigmented rod- to coccoid-shaped coryneform microorganism was isolated from the blood of a patient with acute myeloid leukemia. It was identified by 16S rRNA gene sequencing as a previously undescribed species of Janibacter. The isolate was susceptible to penicillins, aminoglycosides, fluoroquinolones, and glycopeptides. 相似文献
38.
Clinical Features of Fatal Familial Insomnia: Phenotypic Variability in Relation to a Polymorphism at Codon 129 of the Prion Protein Gene 总被引:2,自引:0,他引:2
Pasquale Montagna Pietro Cortelli Patrizia Avoni Paolo Tinuper Giuseppe Plazzi Roberto Gallassi Francesco Portaluppi Jean Julien Claude Vital Marie Bernadette Delisle Pierluigi Gambetti Elio Lugaresi . 《Brain pathology (Zurich, Switzerland)》1998,8(3):515-520
Fatal Familial Insomnia is a hereditary prion disease characterized by a mutation at codon 178 of the prion protein gene cosegregating with the methionine polymorphism at codon 129 of the mutated allele. It is characterized by disturbances of the wake-sleep cycle, dysautonomia and somatomotor manifestations (myoclonus, ataxia, dysarthria, spasticity). PET studies disclose severe thalamic and additionally cortical hypometabolism. Neuropathology shows marked neuronal loss and gliosis in the thalamus, especially the medio-dorsal and anterior-ventral nuclei, olivary hypertrophy and some spongiosis of the cerebral cortex. Detailed analysis of 14 cases from 5 unrelated families showed that patients ran either a short (9.1+ 1.1 months) or a prolonged (30.8 + 21.3 months) clinical course according to whether they were homozygote met/met or heterozygote met/val at codon 129. Moreover, homozygotes had more prominent oneiric episodes, insomnia and dysautonomia at onset, whereas heterozygotes showed ataxia and dysarthria at onset, earlier sphincter loss and epileptic Grand Mai seizures; they also displayed more extensive cortical involvement on PET and at postmortem examination. Our data suggest that the phenotype expression of Fatal Familial Insomnia is related, at least partly, to the polymorphism at codon 129 of the prion protein-gene. 相似文献
39.
Molecular cloning, expression and in situ hybridization of rat brain glutamic acid decarboxylase messenger RNA 总被引:8,自引:0,他引:8
A cDNA library was generated in the expression vector lambda GT11 from rat brain poly(A)+ RNAs and screened with a GAD antiserum. Two clones reacted positively. One of them was shown to express a GAD activity which was specifically trapped on anti-GAD immunogel and was inhibited by gamma-acetylenic-GABA. Blot hybridization analysis of RNAs from rat brain revealed a single 4 kilobases band. Preliminary in situ hybridizations showed numerous cells labelled by the GAD probe such as the Purkinje and stellate cells in the cerebellar cortex and the cells of the reticular thalamic nucleus. 相似文献
40.