scholarly journals Molecular genetic classification in Prader-Willi syndrome: a multisite cohort study

2018 ◽  
Vol 56 (3) ◽  
pp. 149-153 ◽  
Author(s):  
Merlin G Butler ◽  
Samantha N Hartin ◽  
Waheeda A Hossain ◽  
Ann M Manzardo ◽  
Virginia Kimonis ◽  
...  
Keyword(s):  
Maternal Age ◽  
Molecular Genetic ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Genetic Condition ◽  
Genetic Classification ◽  
Older Mothers ◽  
Multiplex Ligation Probe Amplification ◽  
Life Threatening ◽  
Recessive Mutant

BackgroundPrader-Willi syndrome (PWS) is due to errors in genomic imprinting. PWS is recognised as the most common known genetic cause of life-threatening obesity. This report summarises the frequency and further characterises the PWS molecular classes and maternal age effects.MethodsHigh-resolution microarrays, comprehensive chromosome 15 genotyping and methylation-specific multiplex ligation probe amplification were used to describe and further characterise molecular classes of maternal disomy 15 (UPD15) considering maternal age.ResultsWe summarised genetic data from 510 individuals with PWS and 303 (60%) had the 15q11-q13 deletion; 185 (36%) with UPD15 and 22 (4%) with imprinting defects. We further characterised UPD15 findings into subclasses based on the presence (size, location) or absence of loss of heterozygosity (LOH). Additionally, significantly older mothers (mean age=32.5 years vs 27.7 years) were found in the UPD15 group (n=145) compared with the deletion subtype (n=200).ConclusionsWe report on molecular classes in PWS using advanced genomic technology in the largest cohort to date. LOH patterns in UPD15 may impact the risk of having a second genetic condition if the mother carries a recessive mutant allele in the isodisomic region on chromosome 15. The risk of UPD15 may also increase with maternal age.

scholarly journals Prader–Willi syndrome: clinical genetics, cytogenetics and molecular biology

2005 ◽  
Vol 7 (14) ◽  
pp. 1-20 ◽  
Author(s):  
Douglas C. Bittel ◽  
Merlin G. Butler
Keyword(s):  
Clinical Presentation ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Molecular Genetic ◽  
Clinical Genetics ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Future Directions ◽  
Life Threatening ◽  
Genetic Mechanisms

Prader–Willi syndrome (PWS) is a neurodevelopmental disorder that arises from lack of expression of paternally inherited genes known to be imprinted and located in the chromosome 15q11-q13 region. PWS is considered the most common syndromal cause of life-threatening obesity and is estimated at 1 in 10 000 to 20 000 individuals. A de novo paternally derived chromosome 15q11-q13 deletion is the cause of PWS in about 70% of cases, and maternal disomy 15 accounts for about 25% of cases. The remaining cases of PWS result either from genomic imprinting defects (microdeletions or epimutations) of the imprinting centre in the 15q11-q13 region or from chromosome 15 translocations. Here, we describe the clinical presentation of PWS, review the current understanding of causative cytogenetic and molecular genetic mechanisms, and discuss future directions for research.

scholarly journals Multicentre study of maternal and neonatal outcomes in individuals with Prader-Willi syndrome

2018 ◽  
Vol 55 (9) ◽  
pp. 594-598 ◽  
Author(s):  
Preeti Singh ◽  
Ranim Mahmoud ◽  
June-Anne Gold ◽  
Jennifer L Miller ◽  
Elizabeth Roof ◽  
...  
Keyword(s):  
General Population ◽  
Maternal Age ◽  
Genetic Disorder ◽  
Research Network ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Perinatal Complications ◽  
Feeding Difficulties ◽  
Genetic Subtypes ◽  
Pregnancy Weight

IntroductionPrader-Willi syndrome (PWS) is a complex genetic disorder associated with three different genetic subtypes: deletion of the paternal copy of 15q11-q13, maternal UPD for chromosome 15 and imprinting defect. Patients are typically diagnosed because of neonatal hypotonia, dysmorphism and feeding difficulties; however, data on the prenatal features of PWS are limited.ObjectiveThe aim of the study was to identify and compare frequencies of prenatal and neonatal clinical features of PWS among the three genetic subtypes.MethodsData from 355 patients with PWS from the Rare Diseases Clinical Research Network PWS registry were used to analyse multiple maternal and neonatal factors collected during an 8-year multisite study.ResultsAmong our cohort of 355 patients with PWS (61% deletion, 36% UPD and 3% imprinting defect) 54% were born by caesarean section, 26% were born prematurely and 34% with a low birth weight (frequencies 32%, 9.6% and 8.1%, respectively, in the general population). Fetal movements were reported as decreased in 72%. All babies were hypotonic, and 99% had feeding difficulties. Low Apgar scores (<7) were noted in 17.7% and 5.6% of patients, respectively, compared with 1% and 1.4%, respectively, in the general population. Maternal age and pre-pregnancy weight were significantly higher in the UPD group (p=0.01 and <0.001, respectively).ConclusionWe found a higher rate of perinatal complications in PWS syndrome compared with the general population. No significant differences in the genetic subtypes were noted except for a higher maternal age and pre-pregnancy weight in the UPD subgroup

Maternal age at birth and daughter’s fecundability

2021 ◽  
Author(s):  
Olga Basso ◽  
Sydney K Willis ◽  
Elizabeth E Hatch ◽  
Ellen M Mikkelsen ◽  
Kenneth J Rothman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Maternal Age ◽  
Limited Information ◽  
Loss To Follow Up ◽  
Older Mothers ◽  
Registration Number ◽  
The Usa ◽  
Competing Interest

Abstract STUDY QUESTION Do daughters of older mothers have lower fecundability? SUMMARY ANSWER In this cohort study of North American pregnancy planners, there was virtually no association between maternal age ≥35 years and daughters’ fecundability. WHAT IS KNOWN ALREADY Despite suggestive evidence that daughters of older mothers may have lower fertility, only three retrospective studies have examined the association between maternal age and daughter’s fecundability. STUDY DESIGN, SIZE, DURATION Prospective cohort study of 6689 pregnancy planners enrolled between March 2016 and January 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS Pregnancy Study Online (PRESTO) is an ongoing pre-conception cohort study of pregnancy planners (age, 21-45 years) from the USA and Canada. We estimated fecundability ratios (FR) for maternal age at the participant’s birth using multivariable proportional probabilities regression models. MAIN RESULTS AND THE ROLE OF CHANCE Daughters of mothers ≥30 years were less likely to have previous pregnancies (or pregnancy attempts) or risk factors for infertility, although they were more likely to report that their mother had experienced problems conceiving. The proportion of participants with prior unplanned pregnancies, a birth before age 21, ≥3 cycles of attempt at study entry or no follow-up was greater among daughters of mothers &lt;25 years. Compared with maternal age 25–29 years, FRs (95% CI) for maternal age &lt;20, 20–24, 30–34, and ≥35 were 0.72 (0.61, 0.84), 0.92 (0.85, 1.00), 1.08 (1.00, 1.17), and 1.00 (0.89, 1.12), respectively. LIMITATIONS, REASONS FOR CAUTION Although the examined covariates did not meaningfully affect the associations, we had limited information on the participants’ mother. Differences by maternal age in reproductive history, infertility risk factors and loss to follow-up suggest that selection bias may partly explain our results. WIDER IMPLICATIONS OF THE FINDINGS Our finding that maternal age 35 years or older was not associated with daughter’s fecundability is reassuring, considering the trend towards delayed childbirth. However, having been born to a young mother may be a marker of low fecundability among pregnancy planners. STUDY FUNDING/COMPETING INTEREST(S) PRESTO was funded by NICHD Grants (R21-HD072326 and R01-HD086742) and has received in-kind donations from Swiss Precision Diagnostics, FertilityFriend.com, Kindara.com, and Sandstone Diagnostics. Dr Wise is a fibroid consultant for AbbVie, Inc. TRIAL REGISTRATION NUMBER n/a

‘Severe’ Prader-Willi syndrome with a large deletion of chromosome 15 due to an unbalanced t(15,22)(q14;q11.2) translocation

2002 ◽  
Vol 63 (1) ◽  
pp. 79-81 ◽  
Author(s):  
M Matsumura ◽  
T Kubota ◽  
E Hidaka ◽  
K Wakui ◽  
S Kadowaki ◽  
...  
Keyword(s):  
Large Deletion ◽  
Chromosome 15 ◽  
Prader Willi Syndrome

Birth seasonality in Prader-Willi syndrome resulting from chromosome 15 microdeletion

2013 ◽  
Vol 161 (6) ◽  
pp. 1495-1497 ◽  
Author(s):  
Tadayuki Ayabe ◽  
Keiko Matsubara ◽  
Tsutomu Ogata ◽  
Atsuko Ayabe ◽  
Nobuyuki Murakami ◽  
...  
Keyword(s):  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Birth Seasonality

scholarly journals Malignant otitis externa in a 21-year-old male patient with Prader–Willi syndrome

2019 ◽  
Vol 7 ◽  
pp. 2050313X1983482
Author(s):  
Marcos Frata Rihl ◽  
Felipe Marchiori Bau ◽  
Igor de Oliveira ◽  
Manoela Astolfi Vivan ◽  
Roseane Cardoso Marchiori
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Male Patient ◽  
Otitis Externa ◽  
Invasive Infection ◽  
Prader Willi Syndrome ◽  
Malignant Otitis Externa ◽  
Life Threatening

Malignant otitis externa is an invasive infection of the external auditory canal and temporal bone with potentially life-threatening complications. Elderly patients with type 2 diabetes mellitus are the population most commonly affected by malignant otitis externa, but any type of immunosuppression predisposes to the disease. Prader–Willi syndrome is a genetic cause of obesity, often associated with insulin resistance and type 2 diabetes mellitus. This report describes a case of a 21-year-old male patient with Prader–Willi syndrome who had malignant otitis externa that progressed to sepsis during hospitalization. To the best of the authors’ knowledge, this is the first description of malignant otitis externa in a young patient with Prader–Willi syndrome.

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