Syndromic diabetes and hypergonadotropic hypogonadism in a boy with a 12q24.31-32 chromosomal deletion involving HNF1A, DHX37, and SETD1B.

Chromosomal deletions involving several disease-associated genes exhibit diverse phenotypes. HNF1A is one of the causative genes of maturity-onset diabetes of the young. Furthermore, heterozygous variants in DHX37 and SETD1B, located near HNF1A, cause 46,XY disorders of sex development and syndromic neurodevelopmental disorders, respectively. This study describes a 12-yr-old boy with a 12q24.31-32 chromosomal deletion involving HNF1A, DHX37, and SETD1B. The boy was born small-for-gestational age, and experienced seizures, autism spectrum disorder, hearing loss, short stature, and intellectual disability. At five years of age, an 8.6-Mb chromosomal deletion at 12q24.31-32 was identified by array-based comparative genomic hybridization. At 12 yr of age, he developed islet autoantibody-negative diabetes. As the deletion region identified included HNF1A, this suggested that it is a cause of diabetes. Furthermore, SETD1B was considered to be a cause of intellectual disability and autism spectrum disorder. Owing to his intellectual disability, self-management of hypoglycemia was challenging; thus, nateglinide and insulin therapy were deemed effective for diabetes management rather than sulfonylurea drugs. Furthermore, DHX37 haploinsufficiency was considered a cause of hypogonadism. These findings emphasize the importance of diabetes management tailored to the characteristics of children with intellectual disabilities and the potential for hypogonadism due to DHX37 haploinsufficiency.