Craniofacial abnormalities and developmental delay in two families with overlapping 22q12.1 microdeletions involving the MN1 gene

Megan Beck, Jess F. Peterson, Juliann Mcconnell, Marianne Mcguire, Miya Asato, Joseph E. Losee, Urvashi Surti, Suneeta Madan-Khetarpal, Aleksandar Rajkovic, Svetlana A. Yatsenko

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Abstract

Deletions spanning the MN1 gene (22q12.1) have recently been proposed as playing a role in craniofacial abnormalities that include cleft palate, as mouse studies have demonstrated that Mn1 haploinsufficiency results in skull abnormalities and secondary cleft palate. We report on four patients (two families) with craniofacial abnormalities and intellectual disability with overlapping microdeletions that span the MN1 gene. Comparative genomic hybridization microarray analysis revealed a 2.76Mb deletion in the 22q12.1 region, in three family members (Family 1), that contains the MN1 gene. In addition, a complex 22q12 rearrangement, including a 1.61Mb deletion containing the MN1 gene and a 2.28Mb deletion encompassing the NF2 gene, has been identified in another unrelated patient (Family 2). Based upon genotype-phenotype correlation among our patients and those previously reported with overlapping 22q12 deletions, we identified a 560kb critical region containing the MN1 gene that is implicated in human cleft palate formation. Importantly, NF2 was also found within the 22q12 deletion region in several patients which enabled specific clinical management for neurofibromatosis 2.

Original languageEnglish (US)
Pages (from-to)1047-1053
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume167
Issue number5
DOIs
StatePublished - May 1 2015

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Craniofacial Abnormalities
Cleft Palate
Genes
Neurofibromatosis 2
Haploinsufficiency
Comparative Genomic Hybridization
Genetic Association Studies
Microarray Analysis
Skull
Intellectual Disability

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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Craniofacial abnormalities and developmental delay in two families with overlapping 22q12.1 microdeletions involving the MN1 gene. / Beck, Megan; Peterson, Jess F.; Mcconnell, Juliann; Mcguire, Marianne; Asato, Miya; Losee, Joseph E.; Surti, Urvashi; Madan-Khetarpal, Suneeta; Rajkovic, Aleksandar; Yatsenko, Svetlana A.

In: American Journal of Medical Genetics, Part A, Vol. 167, No. 5, 01.05.2015, p. 1047-1053.

Research output: Contribution to journalArticle

Beck, M, Peterson, JF, Mcconnell, J, Mcguire, M, Asato, M, Losee, JE, Surti, U, Madan-Khetarpal, S, Rajkovic, A & Yatsenko, SA 2015, 'Craniofacial abnormalities and developmental delay in two families with overlapping 22q12.1 microdeletions involving the MN1 gene', American Journal of Medical Genetics, Part A, vol. 167, no. 5, pp. 1047-1053. https://doi.org/10.1002/ajmg.a.36839
Beck, Megan ; Peterson, Jess F. ; Mcconnell, Juliann ; Mcguire, Marianne ; Asato, Miya ; Losee, Joseph E. ; Surti, Urvashi ; Madan-Khetarpal, Suneeta ; Rajkovic, Aleksandar ; Yatsenko, Svetlana A. / Craniofacial abnormalities and developmental delay in two families with overlapping 22q12.1 microdeletions involving the MN1 gene. In: American Journal of Medical Genetics, Part A. 2015 ; Vol. 167, No. 5. pp. 1047-1053.
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