How to Cite this Article: Burkardt DD', Rosenfeld JA, Helgeson ML, Angle B, Banks V, Smith WE, Gripp KW, Moline J, Moran RT, Niyazov DM, Stevens CA, Zackai E, Lebel RR, Ashley DG, Kramer N, Lachman RS, Graham Jr. JM. 2011. Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25. Am J Med Genet Part A 155:1336–1351.
Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25†
Article first published online: 5 MAY 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 6, pages 1336–1351, June 2011
How to Cite
Burkardt, D. D., Rosenfeld, J. A., Helgeson, M. L., Angle, B., Banks, V., Smith, W. E., Gripp, K. W., Moline, J., Moran, R. T., Niyazov, D. M., Stevens, C. A., Zackai, E., Lebel, R. R., Ashley, D. G., Kramer, N., Lachman, R. S. and Graham, J. M. (2011), Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25. Am. J. Med. Genet., 155: 1336–1351. doi: 10.1002/ajmg.a.34049
- Issue published online: 20 MAY 2011
- Article first published online: 5 MAY 2011
- Manuscript Accepted: 20 MAR 2011
- Manuscript Received: 19 NOV 2010
- chromosome deletion 1q24-q25;
- intrauterine growth deficiency;
- proportionate short stature;
- cognitive deficiency;
- speech deficiency;
- dysmorphic features
Reports of individuals with deletions of 1q24 q25 share common features of prenatal onset growth deficiency, microcephaly, small hands and feet, dysmorphic face and severe cognitive deficits. We report nine individuals with 1q24q25 deletions, who show distinctive features of a clinically recognizable 1q24q25 microdeletion syndrome: prenatal-onset microcephaly and proportionate growth deficiency, severe cognitive disability, small hands and feet with distinctive brachydactyly, single transverse palmar flexion creases, fifth finger clinodactyly and distinctive facial features: upper eyelid fullness, small ears, short nose with bulbous nasal tip, tented upper lip, and micrognathia. Radiographs demonstrate disharmonic osseous maturation with markedly delayed bone age. Occasional features include cleft lip and/or palate, cryptorchidism, brain and spinal cord defects, and seizures. Using oligonucleotide-based array comparative genomic hybridization, we defined the critical deletion region as 1.9 Mb at 1q24.3q25.1 (chr1: 170,135,865–172,099,327, hg18 coordinates), containing 13 genes and including CENPL, which encodes centromeric protein L, a protein essential for proper kinetochore function and mitotic progression. The growth deficiency in this syndrome is similar to what is seen in other types of primordial short stature with microcephaly, such as Majewski osteodysplastic primordial dwarfism, type II (MOPD2) and Seckel syndrome, which result from loss-of-function mutations in genes coding for centrosomal proteins. DNM3 is also in the deleted region and expressed in the brain, where it participates in the Shank–Homer complex and increases synaptic strength. Therefore, DNM3 is a candidate for the cognitive disability, and CENPL is a candidate for growth deficiency in this 1q24q25 microdeletion syndrome. © 2011 Wiley-Liss, Inc.