Absence of skeletal anomalies in siblings with a maternally inherited 12q13.13-q13.2 microdeletion partially involving the HOXC gene cluster.
Microdeletions (12q13.13-q13.2) involving the HOXC gene cluster are rare. Only three patients with this contiguous deletion have been reported, all resulting in phenotypic features that include skeletal anomalies, facial dysmorphism, and intellectual disability. The deletion of the HOXC gene cluster is thought to result in skeletal anomalies in these patients. We report on siblings with a 969 kb deletion in the 12q13.13-q13.2 region detected by array comparative genomic hybridization (aCGH). This deletion spans seven of nine HOXC cluster genes. FISH analysis confirmed the siblings and mother were carriers of the 12q13.13-q13.2 deletion. Although minor facial dysmorphic features were present in both siblings, no skeletal anomalies were present in the siblings or the mother. The proband had autistic-like features and mild developmental delay, while the sibling and mother are of normal intelligence. The absence of skeletal anomalies in our family suggests that deletion of the entire HOXC gene cluster may be required to result in an abnormal skeletal phenotype, or those skeletal anomalies in previously reported patients may be attributed to other genes within the deletion interval.
Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, Pennsylvania; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
Jess F
JF
Peterson
Jessica
J
Hartman
Lina
L
Ghaloul-Gonzalez
Urvashi
U
Surti
Jie
J
Hu
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D002675:Child, Preschool; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12; D055028:Comparative Genomic Hybridization; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D005810:Multigene Family; D010641:Phenotype; D035781:Siblings
D018398:Homeodomain Proteins
12q13; 12q13.13; 12q13.2; HOX; HOXC; array comparative genomic hybridization (aCGH); microdeletion