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. 2011 Dec;130(6):777-87.
doi: 10.1007/s00439-011-1020-y. Epub 2011 Jun 14.

The role of the TCF4 gene in the phenotype of individuals with 18q segmental deletions

Minire Hasi  1 , Bridgette Soileau, Courtney Sebold, Annice Hill, Daniel E Hale, Louise O'Donnell, Jannine D Cody
Affiliations

The role of the TCF4 gene in the phenotype of individuals with 18q segmental deletions

Minire Hasi et al. Hum Genet. 2011 Dec.

Abstract

The goal of this study is to define the effects of TCF4 hemizygosity in the context of a larger segmental deletion of chromosome 18q. Our cohort included 37 individuals with deletions of 18q. Twenty-seven had deletions including TCF4 (TCF4 (+/-)); nine had deletions that did not include TCF4 (TCF4 (+/+)); and one individual had a microdeletion that included only the TCF4 gene. We compared phenotypic data from the participants' medical records, survey responses, and in-person evaluations. Features unique to the TCF4 (+/-) individuals included abnormal corpus callosum, short neck, small penis, accessory and wide-spaced nipples, broad or clubbed fingers, and sacral dimple. The developmental data revealed that TCF4 (+/+) individuals were only moderately developmentally delayed while TCF4 (+/-) individuals failed to reach developmental milestones beyond those typically acquired by 12 months of age. TCF4 hemizygosity also conferred an increased risk of early death principally due to aspiration-related complications. Hemizygosity for TCF4 confers a significant impact primarily with regard to cognitive and motor development, resulting in a very different prognosis for individuals hemizygous for TCF4 when compared to individuals hemizygous for other regions of distal 18q.

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Figures

Fig. 1
Fig. 1
Panel a Chromosome 18 ideogram. The box indicates the region of the chromosome shown in panels b–d. Panels b–d Display the aCGH data from study participants with distal 18q deletions. The light bars indicated the presence of the intact chromosome. The dark band at the end of the light bar indicated the breakpoint region. The participant’s study number is to the left of their data. Panel b Individuals with terminal deletions of 18q, who have one copy of TCF4. Panel c Individuals with interstitial deletions of 18q who have one copy of TCF4. Panel d The nine individuals in our study cohort with terminal deletions and breakpoints closest to but not including TCF4. These individuals phenotypic data were used as the comparison group
Fig. 2
Fig. 2
Individuals with terminal deletions of 18q, who have one copy of TCF4. a 3 years 9 months, b 6 years, c 6 years 8 months, d 8 years 4 months, e 4 months 29 days, f 9 months, g 14 months 22 days. Individuals with interstitial deletions of 18q who have one copy of TCF4. h 19 years 10 months, i 4 years, j 1 year 5 months, k 4 years 2 months, l 2 years 8 months, m 1 year 10 months. Individuals with terminal deletions and breakpoints closest to but not including TCF4. n 25 years 9 months, o 14 years, p 7 years 5 months, q 8 years 9 months, r 6 years 6 months, s 1 year 2 months. One individual with a small interstitial deletion that includes only the TCF4 gene. t 12 years 8 months
Fig. 3
Fig. 3
Current age and age at death. The open circles indicate current age and the black diamonds indicate the age at death. TCF4+/+; data from 132 individuals with simple distal 18q deletions. Average current age of those with two copies of TCF4 is 17 years. The two individuals in this group who died were a female age 20 years, 6 months and a male 19 years, 9 months. TCF4+/− data from 22 subjects average current age is 11.5 years. Average age at death was 12 years old. The five participants who died included two males and three females; ages 22 months, 6 years 10 months, 13 years, 20 years 11 months, and 22 years
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