Proband

Alex Davey

CN: child loss

Pediatric disorders include a range of highly penetrant, genetically heterogeneous conditions amenable to genomewide diagnostic approaches
[Pediatric. adj. relating to the branch of medicine dealing with children and their diseases]
We had a child –

A total of 13,449 probands were included in the analyses
[Proband. n. (genetics): person serving as the starting point for the genetic study of a family]
His name was Benjamin.

Exome sequencing and microarray data … were complemented by rich clinical phenotypes
[Phenotype. n. (biology): the set of observable characteristics of an individual resulting from the interaction of its genotype with the environment]
Soft curling hair, Mum’s eyes, Dad’s nose, velvet cheeks, chubby feet, huge lopsided smile

Eligibility criteria included … neurodevelopmental disorders, congenital anomalies, abnormal growth measurements, dysmorphic features, unusual behavioral phenotypes, and genetic disorders that have large effects but for which the molecular basis was unknown.
[Disorder. n. (medicine): a disturbance of normal functioning of the mind or body]
Smiling at fairy lights, batting at baubles, following bubbles, reaching for cuddles

Probands were classified as having received a diagnosis if one or more variants or two or more compound heterozygous variants were annotated as pathogenic or likely pathogenic by either the proband’s referring clinician or according to the predicted classification and if the contribution to the phenotype was not clinically annotated as “none.”
[Variant. n. (genetics): An alteration from the most common DNA nucleotide sequence]
He played Joseph in the Nativity, baked cookies for his sisters, went canoeing on a beanbag, enjoyed a good disco, promised his Beaver promise. He saw how leaves filter the sunlight and listened to the rhythm of the rain. He loved unconditionally. He taught me to dream

Factors that considerably increased the chance of receiving a diagnosis included: the presence of severe intellectual disability or developmental delay, longer time interval since recruitment, being the only affected family member…
All members of the family were affected

Through its genomic analysis of a large clinical cohort (each with gifts and talents, needs and desires, friends and families, hopes and ambitions) this study shows how the fusion of clinical expertise, genomic science, and bioinformatics (tolerant patients and trusting parents) can drive diagnosis and discovery in families in which standard, phenotypically driven diagnostic approaches have failed.
In which love, learning and tenacity have triumphed

We thank the patients and families involved in the study.
His name was Benjamin.

The Science

This poem began life as response to a paper on the genomic diagnosis of rare paediatric diseases in New England Journal of Medicine. The paper describes positive advances towards understanding of genetic disease based on the study of c. 13,500 families touched by developmental differences, using exome sequencing and microarray analyses to investigate the genetic causes of disease, and achieving a diagnosis in a remarkable 41% of patients. However, I was struck by the impersonal language used (e.g., proband instead of person; phenotype instead of features; …) which seems to distance the paper from the real people and experiences about which it is written, and from the impacts of the work upon their lives. I wrote this poem in an attempt to re-establish a link between genomic science and its subjects, using details from the life of one such patient – my son. The author is greatly indebted to Dr Rich Gorman and Dr Bobbie Farsides of the Wellcome Trust-funded ‘Ethical Preparedness in Genomic Medicine’ project at Brighton and Sussex Medical School and the University of Oxford, and to poetry tutor Dawn Gorman.

The Poet

Alex Davey (she/her) is a botanist and writer gratefully translocated from the London suburbs to the east coast of Scotland. She is married with two daughters and a son, Benji, who passed away from an undiagnosed genetic disorder at the age of seven. She loves gardening, paddle-boarding and her two greedy guinea pigs.

Next poem: rivers in our houses by Heidi Mendoza