Variants in HNRNPH2 on the X chromosome are associated with a neurodevelopmental disorder in females

Original research article by J.M. Bain et al. (2016)

Read the abstract here.

Using whole-exome sequencing of nearly 5,000 males and females, the researchers were able to identify six females with changes in the HNRNPH2 gene, which is closely associated with development. The HNRNPH2 gene is located on the X chromosome; one X chromosome together with one Y chromosome determine that the person will be male. Males with this genetic change (who only have one copy of the X chromosome) may be too severely affected to survive past early embryonic development. Ranging from age 2 to age 34, all six females identified have genetic changes not found in either of their parents and exhibit intellectual disability or developmental delay, low muscle tone, and differences in facial features. Other clinical features were observed as outlined below.

Clinical Features Observed	Number of Individuals with Feature (out of 6)
Developmental delay/Intellectual Disability	6/6
Loss of an acquired ability or function (developmental regression)	4/6
Autism Spectrum Disorder (ASD)	3/6
Attention-Deficit Hyperactivity Disorder	2/6
Other psychiatric features/diagnoses (such as anxiety, aggression)	3/6
Seizures	3/6
Muscle weakness (hypotonia)	6/6
Muscle spasms (hypertonia)	1/6
Abnormally small head due to improper brain development (microcephaly)	2/6
Subtle differences in physical features (dysmorpisms), full lips, wide mouth, highly arched palate	6/6
Skeletal abnormalities (such as short stature, curvature of the spine, flat feet)	4/6
Gastrointestinal or growth problems	6/6
Cardiac issues	2/6