Background:
Copy number variants (CNVs) associated with developmental delay and intellectual disability (DD/ID) continue to be identified in patients. This article reports identification of a chromosome 1q22 microdeletion as the genetic cause in a Chinese family affected by ID.
Case presentation:
The proband was a 19-year-old pregnant woman referred for genetic counseling and prenatal diagnosis at 18 weeks of gestation. She had severe ID with basically normal stature (height 154 cm [0 SD], weight 61 kg [- 0.2 SD], and head circumference 54 cm [- 1.12 SD]). Her distinctive facial features included a prominent forehead; flat face; flat nasal bridge and a short upturned nose; thin lips; and small ears. The proband's father was reported to have low intelligence, whereas her mother was of normal intelligence but with scoliosis. Chromosome microarray analysis (CMA) reveals that the proband, her father and the fetus all carry a 1q22 microdeletion of 936.3 Kb (arr[GRCh37] 1q22 (155016052_155952375)×1), which was not observed in her mother and paternal grandparents and uncles, suggesting a de novo mutation in the proband's father. The microdeletion involves 24 OMIM genes including ASH1L (also known as KMT2H and encoding a histone lysine methyltransferase). Of note, haploinsufficiency of ASH1L has been shown to be associated with neurodevelopmental disorders. Based on the inheritance of the detected CNV in the pedigree and similar CNVs associated with ID in public databases (Decipher, DGV and ClinVar) and literature, the detected CNV is considered as pathogenic. The family chose to terminate the pregnancy.
Conclusions:
The identified 1q22 microdeletion including ASH1L is pathogenic and associated with ID. This case broadens the spectrum of ID-related CNVs and may be useful as a reference for clinicians.