Consequences of chromsome18q deletions

Jannine D. Cody, Courtney Sebold, Patricia Heard, Erika Carter, Bridgette Soileau, Minire Hasi-Zogaj, Annice Hill, David Rupert, Brian Perry, Louise O'Donnell, Jon Gelfond, Jack Lancaster, Peter T. Fox, Daniel Hale

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Providing clinically relevant prognoses and treatment information for people with a chromsome18q deletion is particularly challenging because every unrelated person has a unique region of hemizygosity. The hemizygous region can involve almost any region of 18q including between 1 and 101 genes (30Mb of DNA). Most individuals have terminal deletions, but in our cohort of over 350 individuals 23% have interstitial deletions. Because of this heterogeneity, we take a gene by gene approach to understanding the clinical consequences. There are 196 genes on 18q. We classified 133 of them as dosage insensitive, 15 (8%) as dosage sensitive leading to haploinsufficiency while another 10 (5%) have effects that are conditionally haploinsufficient and are dependent on another factor, genetic or environmental in order to cause an abnormal phenotype. Thirty-seven genes (19%) have insufficient information to classify their dosage effect. Phenotypes attributed to single genes include: congenital heart disease, minor bone morphology changes, central nervous system dysmyelination, expressive speech delay, vesicouretreral reflux, polyposis, Pitt-Hopkins syndrome, intellectual disability, executive function impairment, male infertility, aural atresia, and high frequency sensorineural hearing loss. Additionally, identified critical regions for other phenotypes include: adolescent idiopathic scoliosis and pectus excavatum, Virchow-Robin perivascular spaces, small corpus callosum, strabismus, atopic disorders, mood disorder, IgA deficiency, nystagmus, congenital heart disease, kidney malformation, vertical talus, CNS dysmyelination growth hormone deficiency and cleft palate. Together these findings make it increasingly feasible to compile an individualized syndrome description based on each person's individuated genotype. Future work will focus on understanding molecular mechanisms leading to treatment.

Original languageEnglish (US)
Pages (from-to)265-280
Number of pages16
JournalAmerican Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Volume169
Issue number3
DOIs
StatePublished - Sep 1 2015

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Genes
Phenotype
Heart Diseases
Congenital Nystagmus
High-Frequency Hearing Loss
IgA Deficiency
Flatfoot
Funnel Chest
Language Development Disorders
Haploinsufficiency
Songbirds
Sensorineural Hearing Loss
Corpus Callosum
Strabismus
Male Infertility
Executive Function
Cleft Palate
Scoliosis
Mood Disorders
Intellectual Disability

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Cody, Jannine D. ; Sebold, Courtney ; Heard, Patricia ; Carter, Erika ; Soileau, Bridgette ; Hasi-Zogaj, Minire ; Hill, Annice ; Rupert, David ; Perry, Brian ; O'Donnell, Louise ; Gelfond, Jon ; Lancaster, Jack ; Fox, Peter T. ; Hale, Daniel. / Consequences of chromsome18q deletions. In: American Journal of Medical Genetics, Part C: Seminars in Medical Genetics. 2015 ; Vol. 169, No. 3. pp. 265-280.
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Cody, JD, Sebold, C, Heard, P, Carter, E, Soileau, B, Hasi-Zogaj, M, Hill, A, Rupert, D, Perry, B, O'Donnell, L, Gelfond, J, Lancaster, J, Fox, PT & Hale, D 2015, 'Consequences of chromsome18q deletions', American Journal of Medical Genetics, Part C: Seminars in Medical Genetics, vol. 169, no. 3, pp. 265-280. https://doi.org/10.1002/ajmg.c.31446

Consequences of chromsome18q deletions. / Cody, Jannine D.; Sebold, Courtney; Heard, Patricia; Carter, Erika; Soileau, Bridgette; Hasi-Zogaj, Minire; Hill, Annice; Rupert, David; Perry, Brian; O'Donnell, Louise; Gelfond, Jon; Lancaster, Jack; Fox, Peter T.; Hale, Daniel.

In: American Journal of Medical Genetics, Part C: Seminars in Medical Genetics, Vol. 169, No. 3, 01.09.2015, p. 265-280.

Research output: Contribution to journalArticle

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AU - Hasi-Zogaj, Minire

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AU - Perry, Brian

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AU - Lancaster, Jack

AU - Fox, Peter T.

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Cody JD, Sebold C, Heard P, Carter E, Soileau B, Hasi-Zogaj M et al. Consequences of chromsome18q deletions. American Journal of Medical Genetics, Part C: Seminars in Medical Genetics. 2015 Sep 1;169(3):265-280. https://doi.org/10.1002/ajmg.c.31446