Lee Cc

Recurrent 2q13 microduplication encompassing MALL, NPHP1, RGPD6, and BUB1 associated with autism spectrum disorder, intellectual disability, and liver disorder

OBJECTIVE We present recurrent 2q13 microduplication in a family with autism spectrum disorder (ASD), intellectual disability, and liver disorder. CASE REPORT A 45-year-old woman and her 52-year-old husband were referred for genetic counseling because of mental and liver disorders in their two sons and their planning for prenatal diagnosis of familial disorders in the future pregnancy. She and her husband were normal and healthy, but their 21-year-old elder son had suffered from ASD, severe intellectual disability, poor motor function, liver cirrhosis, and esophageal varices, and their 19-year-old younger son had suffered from ASD, mild intellectual disability, poor balance and coordination, hepatosplenomegaly, fatty liver, and mild liver cirrhosis. The karyotypes of the parents and sons were normal. Array comparative genomic hybridization of the family revealed a 686.5-kb 2q13 microduplication encompassing MALL, NPHP1, RGPD6, and BUB1 in the elder brother, a 658.9-kb 2q13 microduplication encompassing MALL, NPHP1, RGPD6, and BUB1 in the younger brother, and an 83.83-kb 2q13 microduplication encompassing NPHP1 in the asymptomatic father. CONCLUSION Recurrent phenotypic abnormality in the family with normal karyotype should include a differential diagnosis of pathogenic copy-number variations.

Familial transmission of recurrent 15q11.2 (BP1-BP2) microdeletion encompassing NIPA1, NIPA2, CYFIP1, and TUBGCP5 associated with phenotypic variability in developmental, speech, and motor delay

OBJECTIVE We present recurrent 15q11.2 (BP1-BP2) microdeletion encompassing NIPA1, NIPA2, CYFIP1, and TUBGCP5 in a family with phenotypic variability in developmental, speech, and motor delay. CASE REPORT A 32-year-old woman underwent amniocentesis at 17 weeks of gestation because of an abnormal maternal serum screening result of Down syndrome risk of 1/226. Her husband was 31 years old. She and her husband were phenotypically normal, and there was no family history of mental disorders and congenital malformations. Amniocentesis revealed a karyotype of 46,XX. Prenatal ultrasound findings were unremarkable. A 2492-g female baby was delivered at 37 weeks of gestation uneventfully. During the subsequent pregnancy, the same woman at the age of 35 years underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, which revealed a karyotype of 46,XY. Prenatal ultrasound findings were unremarkable. A 2780-g male baby was delivered at 37 weeks of gestation uneventfully. About 3 years after the birth of this boy, array comparative genomic hybridization of the family revealed 15q11.2 microdeletion encompassing NIPA1, NIPA2, CYFIP1, and TUBGCP5 in the two siblings, who displayed developmental, speech, and motor delay, and in their phenotypically normal father. CONCLUSION Recurrent phenotypic abnormality in the family with normal karyotype at amniocentesis should include a differential diagnosis of familial pathogenic copy-number variations.