A familial 7q36.3 duplication associated with agenesis of the corpus callosum

Abstract

Small chromosomal duplications involving 7q36.3 have rarely been reported. This clinical report describes four individuals from a three-generation family with agenesis of the corpus callosum (ACC) and a 0.73 Mb duplication of 7q36.3 detected by array CGH. The 7q36.3 duplication involves two genes: RNA Binding Motif Protein 33 (RBM33) and Sonic Hedgehog (SHH). Most affected family members had mild intellectual disability or borderline intellectual functioning, macrocephaly, a broad forehead, and widely spaced eyes. Two individuals had a Chiari type I malformation. This is the first family reported with ACC associated with a small duplication of these genes. While we cannot establish causation for the relationship between any single gene and the ACC in this family, there is a role for SHH in the formation of the corpus callosum through correct patterning and assembly of the commissural plate, and these data concur with vertebrate studies showing that a gain of SHH expands the facial primordium.

De novo chromosome 7q36.1q36.2 triplication in a child with developmental delay, growth failure, distinctive facial features, and multiple congenital anomalies: a case report

“…Duplications involving the 7q36.3 region have been less frequently reported. Four individuals from a three-generation family were reported with 7q36.3 duplication and intellectual disability, corpus callosum agenesis, Chiari malformation, macrocephaly, and distinctive facial features [ 5 ]. Additionally, 7q36.3 duplications were reported in two siblings with muscle hypertrophy and an infant with encephalocele [ 6 , 7 ].…”

Prenatal identification of two discontinuous maternally inherited chromosome 7q36.3 microduplications totaling 507 kb including the sonic hedgehog gene in a fetus with multiple congenital anomalies

“…Duplications of the SHH gene are rare. A familial 0.73 Mb 7q36.3 duplication involving SHH and RBM33 genes was identified in four individuals from a three-generation family with mild intellectual disability, macrocephaly, and a Chiari I malformation [5]. This study also mentions four other individuals with overlapping 7q36.3 duplications found in the DECIPHER database; however, because the size of these duplications varied, no specific genotype:phenotype correlations were possible.…”

“…Specifically, chromosome 7q duplications involving band 7q36.3 have been rarely reported. Most recently, a three‐generation family with agenesis of the corpus callosum and a 730‐kb duplication of 7q36.3 involving copy number gain of RNA binding motif protein 33 ( RBM33 ) and sonic hedgehog ( SHH ) genes was reported . The phenotype of the affected family members included intellectual disability or borderline intellectual functioning, macrocephaly, a broad forehead with hypertelorism, and Chiari type I malformation.…”

“…The phenotype of these cases is often variable because of the imbalance of another chromosome associated with the rearrangement. In contrast, twenty-two cases of pure partial trisomy 7q have been reported [1][2][3][4][5][6]. Specifically, chromosome 7q duplications involving band 7q36.3 have been rarely reported.…”

Prenatal Diagnosis of Corpus Callosum Agenesis in Four Fetuses

“…The CMA results of Fetus 3 showed there were 8.8M duplication in the 7q36.1q36.3, which contains 51 OMIM genes including SHH, LMBR1, RBM33, etc. The patients with duplication in this area can be pathogenic, including intellectual disability, growth retardation, dysplasia of corpus callosum, special facial features, congenital heart disease and other clinical manifestations [20]. It also have about 6.5M deletions of chromosome 1q43q44 region contains 21 OMIM genes including AKT3, HNRNPU, ZBTB18, etc in Fetus, which is pathogenic, there may be intellectual disability, microcephaly, epilepsy, craniofacial abnormalities and other clinical manifestations [21].…”