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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10360568" target="_blank" >RIV/00216208:11110/17:10360568 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/17:10360568 RIV/00064203:_____/17:10360568 RIV/00064165:_____/17:10360568

Result on the web

<a href="http://dx.doi.org/10.1186/s12881-017-0425-4" target="_blank" >http://dx.doi.org/10.1186/s12881-017-0425-4</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12881-017-0425-4" target="_blank" >10.1186/s12881-017-0425-4</a>

Result language

angličtina

Original language name

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

Original language description

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. Conclusions: 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

Project

<a href="/en/project/NV17-29423A" target="_blank" >NV17-29423A: Analysis of genetic variants associated with intellectual disability and autism spectrum disorders using next generation sequencing</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

BMC Medical Genetics

ISSN

1471-2350

e-ISSN

—

Volume of the periodical

18

Issue of the periodical within the volume

June

Country of publishing house

GB - UNITED KINGDOM

Number of pages

7

Pages from-to

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UT code for WoS article

000402574600003

EID of the result in the Scopus database

2-s2.0-85019993982