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Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland, 2023, Wright et al.

Discussion in 'Other health news and research' started by John Mac, Apr 13, 2023.

  1. John Mac

    John Mac Senior Member (Voting Rights)

    BBC: Thousands of children with severe developmental disorders have finally been given a diagnosis, in a study that found 60 new diseases.

    Children, and their parents, had their genetic code - or DNA - analysed in the search for answers to their condition.

    There are thousands of different genetic disorders.

    Having a diagnosis can lead to better care, help parents to decide whether to have more children, or simply provide an explanation for what is happening.

    Taken individually the disorders are rare, but collectively they affect one in every 17 people in the UK.

    The Deciphering Developmental Disorders study, conducted over 10 years, was a collaboration between the NHS, universities and the Sanger Institute, which specialises in analysing DNA.

    Among the findings, researchers discovered Turnpenny-Fry syndrome. It is caused by errors in one genetic instruction within our DNA and leads to learning difficulties. It also affects growth, resulting in a large forehead and sparse hair.

    Last edited by a moderator: Jun 23, 2023
    merylg, inox, Wits_End and 11 others like this.
  2. John Mac

    John Mac Senior Member (Voting Rights)

    The study:

    Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland


    Pediatric disorders include a range of highly penetrant, genetically heterogeneous conditions amenable to genomewide diagnostic approaches. Finding a molecular diagnosis is challenging but can have profound lifelong benefits.

    We conducted a large-scale sequencing study involving more than 13,500 families with probands with severe, probably monogenic, difficult-to-diagnose developmental disorders from 24 regional genetics services in the United Kingdom and Ireland. Standardized phenotypic data were collected, and exome sequencing and microarray analyses were performed to investigate novel genetic causes. We developed an iterative variant analysis pipeline and reported candidate variants to clinical teams for validation and diagnostic interpretation to inform communication with families. Multiple regression analyses were performed to evaluate factors affecting the probability of diagnosis.

    A total of 13,449 probands were included in the analyses. On average, we reported 1.0 candidate variant per parent–offspring trio and 2.5 variants per singleton proband. With the use of clinical and computational approaches to variant classification, a diagnosis was made in approximately 41% of probands (5502 of 13,449), of whom 76% had a pathogenic de novo variant. Another 22% of probands (2997 of 13,449) had variants of uncertain significance in genes that were strongly linked to monogenic developmental disorders. Recruitment in a parent–offspring trio had the largest effect on the probability of diagnosis (odds ratio, 4.70; 95% confidence interval [CI], 4.16 to 5.31). Probands were less likely to receive a diagnosis if they were born extremely prematurely (i.e., 22 to 27 weeks’ gestation; odds ratio, 0.39; 95% CI, 0.22 to 0.68), had in utero exposure to antiepileptic medications (odds ratio, 0.44; 95% CI, 0.29 to 0.67), had mothers with diabetes (odds ratio, 0.52; 95% CI, 0.41 to 0.67), or were of African ancestry (odds ratio, 0.51; 95% CI, 0.31 to 0.78).

    Among probands with severe, probably monogenic, difficult-to-diagnose developmental disorders, multimodal analysis of genomewide data had good diagnostic power, even after previous attempts at diagnosis. (Funded by the Health Innovation Challenge Fund and Wellcome Sanger Institute.)

    merylg, inox, MEMarge and 7 others like this.
  3. Hutan

    Hutan Moderator Staff Member

    Aotearoa New Zealand
    I thought new diseases weren't supposed to be given a name that includes the names of people?

    Edit - oh, that was a bit negative, I should have also said 'Good news; I'm sure a lot of families will benefit'.
    Last edited: Apr 13, 2023
  4. Arnie Pye

    Arnie Pye Senior Member (Voting Rights)

    Those paediatric patients - assuming their genetic condition doesn't increase the risk of early death - grow up to be adult patients. I wonder if there are there any plans to let adults get tested if they are suspected of having an undiagnosed genetic disease?
  5. Shadrach Loom

    Shadrach Loom Senior Member (Voting Rights)

    London, UK
    It’s a good point, though, and is particularly relevant to us, as an eponym (or toponym) is our best option in the absence of a biomarker.
    Hutan, Wonko and Peter Trewhitt like this.
  6. ukxmrv

    ukxmrv Senior Member (Voting Rights)

    It doesn't seem to be a priority. In my family genetic testing started with a great niece. Sadly for her they had to wait until she was 5. It was obvious from birth but doctors fobbed off my niece. They could have benefitted from early therapy and all that time was wasted with no care or support.

    The genetic condition she has was said to be very rare. Then they found another girl of a similar age on the same small city.

    Next to be tested was a great nephew. Another separate rare genetic test. In this case they tested his father and found the same thing.

    There has been no attempt to test other family members. Seems to take a very long time to get a referral and one has to be very pushy even when it is very obvious.
  7. Wits_End

    Wits_End Senior Member (Voting Rights)

    UK London
    Really? I think I know someone who might qualify.
    Peter Trewhitt likes this.

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