Clinical and molecular characterization of a second case of 7p22.1 microduplication

Abstract

The use of high-resolution microarray technology for investigation of patients with intellectual disability and/or congenital anomalies provided the unique possibility to identify new microdeletion/microduplication syndromes and discover the dosage sensitive genes, which are implicated in the manifestation of various genetic conditions. Microduplication of the 7p22.1 region, 1.7 Mb in size, has very recently been reported, representing the smallest interstitional 7p duplication, associated with specific facial features and speech delay. We report on a patient with an even smaller 7p22.1 de novo microduplication, 1 Mb in size, detected in a 14.5-year-old patient with mild intellectual disability and similar facial dysmorphism, including macrocephaly, ocular hypertelorism, low-set ears, and other features. There are 15 RefSeq genes included in this duplication. ACTB gene is a strong candidate gene for the alteration of craniofacial development. Further cases with similar duplications will contribute to the delineation of a potential new microduplication syndrome of 7p22.1.

Refinement of the critical region in a new 7p22.1 microduplication syndrome including craniofacial dysmorphism and speech delay

“…Facial appearance of propositus at the time of genetic evaluation (3 years). The main clinical features are consistent with the two other cases previously described by Chui et al and Preiksaitiene et al: prominent forehead, hypertelorism, high‐arched eyebrows, downslanted palpebral fissures, anteverted nares, large mouth with thin lips, and ears abnormalities (small ears and narrow external auditory canals) [Chui et al, ; Preiksaitiene et al, ]. [Color figure can be viewed in the online issue, which is available at onlinelibrary.wiley.com/journal/10.1002/(ISSN) 1552‐4833]…”

“…Here, we report on an additional unrelated young boy with a 7p22.1 microduplication contributing to the delineation of this new syndrome. Moreover, this patient significantly refines the minimal critical region highlighted by Preiksaitiene et al, [].…”

“…Recently, in this journal, two children with overlapping apparently de novo 7p22.1 microduplications, characterized by aCGH, have been reported [Chui et al, ; Preiksaitiene et al, ]. They shared clinical features including: speech delay, macrocephaly, widely spaced eyes, anteverted narses, low set ears, and skeletal abnormalities.…”

“…They shared clinical features including: speech delay, macrocephaly, widely spaced eyes, anteverted narses, low set ears, and skeletal abnormalities. Preiksaitiene et al [] suggested that 7p22.1 duplication may constitute a newly recognized clinical syndrome. Here, we report on an additional unrelated young boy with a 7p22.1 microduplication contributing to the delineation of this new syndrome.…”

Multiple copy number variants in a pediatric patient with Hb H disease and intellectual disability

“…Regarding the duplication at 7p21, a 7p duplication syndrome has been described; its common phenotypic features include intellectual disability, hypotonia, large anterior fontanel, high/prominent forehead, microcephaly, hypertelorism, abnormally slanted palpebral fissures, flat nasal bridge, abnormal palate, low‐set ears, skeletal abnormalities and cardiovascular abnormalities [Chui et al, ], as well as autism [Goitia et al, ]. At least 20 cases of “pure” 7p duplications have been previously described [Papadopoulou et al, ], 4 of them microduplications [Chui et al, ; Preiksaitiene et al, ; Pebrel‐Richard et al, ; Goitia et al, ], which allowed to delimit and identify candidate genes, establishing a minimal critical region from 5,337,072 to 5,766,245 (NCBI Build 36) on chromosome 7p22.1, highlighting ACTB as the main candidate gene. Although this region is unaffected in our patient, many CNVs involving 7p22.3‐p22.1, some of them pathogenic, are listed in free databases.…”