↓ Skip to main content

Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1-associated phenotype: case report

Overview of attention for article published in BMC Medical Genetics, June 2017
Altmetric Badge

About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (51st percentile)

Mentioned by

twitter
3 tweeters
facebook
2 Facebook pages

Citations

dimensions_citation
16 Dimensions

Readers on

mendeley
68 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1-associated phenotype: case report
Published in
BMC Medical Genetics, June 2017
DOI 10.1186/s12881-017-0425-4
Pubmed ID
Authors

Darina Prchalova, Marketa Havlovicova, Katalin Sterbova, Viktor Stranecky, Miroslava Hancarova, Zdenek Sedlacek

Abstract

Whole exome sequencing is a powerful tool for the analysis of genetically heterogeneous conditions. The prioritization of variants identified often focuses on nonsense, frameshift and canonical splice site mutations, and highly deleterious missense variants, although other defects can also play a role. The definition of the phenotype range and course of rare genetic conditions requires long-term clinical follow-up of patients. We report an adult female patient with severe intellectual disability, severe speech delay, epilepsy, autistic features, aggressiveness, sleep problems, broad-based clumsy gait and constipation. Whole exome sequencing identified a de novo mutation in the SYNGAP1 gene. The variant was located in the broader splice donor region of intron 10 and replaced G by A at position +5 of the splice site. The variant was predicted in silico and shown experimentally to abolish the regular splice site and to activate a cryptic donor site within exon 10, causing frameshift and premature termination. The overall clinical picture of the patient corresponded well with the characteristic SYNGAP1-associated phenotype observed in previously reported patients. However, our patient was 31 years old which contrasted with most other published SYNGAP1 cases who were much younger. Our patient had a significant growth delay and microcephaly. Both features normalised later, although the head circumference stayed only slightly above the lower limit of the norm. The patient had a delayed puberty. Her cognitive and language performance remained at the level of a one-year-old child even in adulthood and showed a slow decline. Myopathic facial features and facial dysmorphism became more pronounced with age. Although the gait of the patient was unsteady in childhood, more severe gait problems developed in her teens. While the seizures remained well-controlled, her aggressive behaviour worsened with age and required extensive medication. The finding in our patient underscores the notion that the interpretation of variants identified using whole exome sequencing should focus not only on variants in the canonical splice dinucleotides GT and AG, but also on broader splice regions. The long-term clinical follow-up of our patient contributes to the knowledge of the developmental trajectory in individuals with SYNGAP1 gene defects.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 68 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 68 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 11 16%
Student > Ph. D. Student 10 15%
Student > Doctoral Student 10 15%
Researcher 7 10%
Student > Bachelor 5 7%
Other 9 13%
Unknown 16 24%
Readers by discipline Count As %
Psychology 13 19%
Medicine and Dentistry 13 19%
Neuroscience 7 10%
Agricultural and Biological Sciences 5 7%
Nursing and Health Professions 5 7%
Other 8 12%
Unknown 17 25%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 November 2018.
All research outputs
#10,789,334
of 18,800,073 outputs
Outputs from BMC Medical Genetics
#338
of 980 outputs
Outputs of similar age
#131,940
of 281,773 outputs
Outputs of similar age from BMC Medical Genetics
#1
of 1 outputs
Altmetric has tracked 18,800,073 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 980 research outputs from this source. They receive a mean Attention Score of 3.6. This one has gotten more attention than average, scoring higher than 63% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 281,773 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them