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Biomedical subjects

Peter Miny

Publications and source records attributed to Peter Miny.

6 recordsLinked to original sources
PubMed2025

Pathogenic XPO1 variants cause a dominant neurodevelopmental disorder.

PURPOSE: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome; however, no monogenic XPO1-related disorder has been described to date. METHODS: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We used Drosophila to study XPO1 function in development and habituation learning. RESULTS: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants, and half have coding variants (10 missense and 1 in-frame deletion variant). We found an overlapping phenotype, consistent with a monogenic neurodevelopmental disorder. We demonstrate XPO1 functions in development by ubiquitous and neuron-specific knockdown in Drosophila. GABAergic neuron specific knockdown flies demonstrated impaired habituation. CONCLUSION: Our results establish XPO1 as a novel dominant monogenic neurodevelopmental disorder gene and demonstrate a central role for XPO1 in development.

Exportin 1 Protein↗
PubMed2025

Bi-allelic loss-of-function variants in POC5 cause a syndromic retinal, endocrine, and neuromuscular ciliopathy.

PURPOSE: A homozygous loss-of-function (LoF) variant in POC5 was previously described in an individual with retinitis pigmentosa. We identified POC5 variants in 12 probands with a syndromic phenotype. We aim to define the phenotype spectrum and molecular mechanism associated with biallelic POC5 LoF variants. METHODS: We studied a cohort of 12 families with bi-allelic LoF POC5 variants and performed detailed phenotype analysis. POC5 localization studies were performed in 3 proband-derived fibroblast cell lines. RESULTS: Detailed phenotyping of probands with POC5 variants expands the phenotype spectrum beyond ocular manifestations. This syndrome causes not only rod-cone dystrophy but also diabetes mellitus with severe insulin resistance and partial lipodystrophy, kidney disease, and muscle cramps. The POC5 protein plays an essential role during cell cycle and cilium formation. Interestingly, POC5 localization studies in 3 proband-derived fibroblast cell lines show aberrant localization suggesting a ciliary defect. The phenotypes of the 12 families in this study fit well within the ciliopathy phenotype spectrum, except for lipodystrophy, which is not common in ciliopathies. CONCLUSION: We describe a multiorgan syndrome caused by bi-allelic LoF variants in POC5. This underscores the pleiotropic effects of POC5 variants and highlights the significance of adipose tissue and metabolic dysfunction in ciliopathies.

Humans↗
PubMed2006

Postnatal follow-up of prenatally diagnosed trisomy 16 mosaicism.

OBJECTIVE: To determine the long-term outcome of pregnancies prenatally diagnosed with trisomy 16 and identify variables associated with the outcome. METHODS: We reviewed all published and our unpublished data from trisomy 16 pregnancies for which outcomes were available for children of greater than 1 year of age. RESULTS: Nineteen cases were diagnosed with trisomy 16 on chorionic villus sampling (CVS) and 17 cases at amniocentesis. Age at last follow-up ranges from 1 to 13 years. Among the CVS group, four out of five patients, with a birth weight and/or length below -2 SD and postnatal growth information, showed catch-up growth (80%). Among the amniotic fluid (AF) group, the birth weight was available in 13 cases. Eleven of the 13 cases had a birth weight less than -2 SD. In eight cases, the length was also below -2 SD (length data unavailable in one case). Nine out of ten cases (90%) and seven out of eight (87.5%) showed catch-up growth for weight and length, respectively. In terms of development, no cases of CVS mosaicism had global developmental delay. One child had a history of delay in speech development. Among the AF-detected cases, 4/17 cases had global developmental delay. All four children with global developmental delay had more than one major malformation compared to 6 out of 32 children in the group with normal development (p = 0.004). The finding of uniparental disomy (UPD) was not associated with developmental delay. CONCLUSIONS: The majority of prenatally diagnosed trisomy 16 mosaic cases have a good postnatal outcome. However, the finding of mosaicism on AF and the presence of major congenital anomalies are associated with an increased risk of developmental delay.

Amniocentesis↗
PubMed2002

Outcomes of pregnancies diagnosed with Klinefelter syndrome: the possible influence of health professionals.

OBJECTIVE: To describe the association between the outcomes of pregnancies diagnosed with Klinefelter syndrome (KS) and the specialty of the health professional providing pre- and post-diagnostic counselling. METHOD: Data were extracted from the case notes of the 111 cases of KS diagnosed prenatally between 1986 and 1997 in eight geographical regions in five European countries. The data extracted included: outcome of pregnancy, maternal age, social class, parity, gestational age at diagnosis, year of diagnosis and specialties of the health professionals conducting pre- and post-diagnosis consultations. RESULTS: The overall termination rate was 44% (49/111: 95% confidence interval: 35 to 54). Using multivariable logistic regression analysis, the only significant predictor of continuation of the pregnancy was the specialties of the health professionals conducting post-diagnosis counselling: the affected pregnancy was more likely to continue when post-diagnosis counselling involved only a genetics specialist (relative risk: 2.42 (1.14 to 5.92)). CONCLUSION: There is an association between whether or not a woman terminates a pregnancy affected by an unfamiliar fetal anomaly and the professional background of the health professional providing post-diagnostic counselling. The causal nature of this association remains to be determined.

Abortion, Eugenic↗
PubMed2002

Developments in laboratory techniques for prenatal diagnosis.

Ongoing trends in prenatal diagnosis aim at early, rapid, and ideally noninvasive diagnosis as well as at the improvement of risk-screening for aneuploidy. Interphase-fluorescence in situ hybridization and quantitative fluorescence polymerase chain reaction are efficient tools for the rapid exclusion of selected aneuploidies in addition to the established direct preparation of chromosomes from chorionic villi. Interphase fluorescence in situ hybridization has also made possible the diagnosis of selected chromosome abnormalities in single cells (e.g. in preimplantation genetic diagnosis) or noninvasive diagnosis. More complex multicolor fluorescence in situ hybridization approaches are currently being evaluated. Single cell polymerase chain reaction is the key technique for the molecular diagnosis of a growing number of monogenic conditions before implantation or, still more experimental, in fetal cells retrieved from the maternal circulation. New sources for noninvasive diagnosis came into play such as fetal DNA or cell nuclei in maternal plasma. The combination of biochemical parameters in the maternal serum, namely free beta-human chorionic gonadotropin with pregnancy associated plasma protein A and sonographic markers, has already dramatically increased the sensitivity of risk screening in the first trimester of pregnancy.

Amniocentesis↗