ARHGAP4 mutated in a Chinese intellectually challenged family.

Objective: Mental retardation is characterized by lower intelligence compared to the average intelligence of persons the same age. These patients have low adaptive capacity acquired by society. The genetic factors of causing MR include monogenic disease, chromosome structural aberration, and chromosome number aberration and so on. We explored the cause of a Chinese family suffering from mental retardation.

Methods: We used karyotyping technology to determine the karyotype of the proband, and we used FISH to verify the result of the karyotyping. We used whole-exome sequencing to identify the disease-causing gene and used Sanger sequencing to verify the result of whole-exome sequencing to assess the family's gene expression.

Results: The G-banding of the karyotype revealed that the patient's karyotype is 46, XY. FISH revealed that the patient does not have a trisomy syndrome. The karyotype of the proband is normal. Using whole-exome sequencing, we identified 108,767 variants in the exome gene of the patient, including 101,787 SNPs and 6980 InDels. Combining clinical information and bioinformatics analysis, including databases filtering and SIFT analysis, we found ARHGAP4 in X chromosome was candidate MR disease-causing gene. PCR and Sanger sequencing results were consistent with whole-exome sequencing. ARHGAP4 (T491M) mutation was present in the genome of the proband and his mother is a carrier, while his father, sister, and brother do not carry this mutation.

Conclusion: According to clinical information, whole-exome sequencing results and Sanger verification results, ARHGAP4 (T491M) mutation may be disease-causing gene of the MR patient. The relation between ARHGAP4 mutation and MR clinical characteristic is needed to be illuminated with participation of more MR patients.