ESPE Abstracts

Objective: Maturity onset diabetes of the young (MODY)5 is a type of monogenic diabetes. Primary autosomal recessive microcephaly (MCPH)3 is a rare microcephaly caused by depletion of neuronal progenitor cells characterized by mostly normal brain structure, mental retardation, and premature closure of the frontal cranial suture. To report a case of MODY5 combined with MCPH3, in order to increase the clinical attention to this disease.

Methods: The clinical data and genetic testing of the children were analyzed to confirm the diagnosis.

Results: The proband, a 13 years and 5 months girl, admitted to our hospital with "diabetic ketosis". The physical examination was central obesity, microcephaly (48 cm, -4.1SD), and acanthosis nigricans could be seen under the neck and armpit, nervous system examination revealed no abnormality. The child was born naturally at 38 weeks, with normal birth length and weight, and a head circumference of 29 cm (-4.1SD) at birth. There was no history of birth trauma or asphyxia. At the age of 7, it was found that the intellectual development was low, the number was insensitive, and the fine motor was poor. The intellectual evaluation showed the passing level of intellectual development. At present, the fine motor is still poor, and he is studying in the first year of junior high school, and his academic performance is not good. There was no family history of diabetes and microcephaly. Auxiliary examination: Diabetic antibodies were negative, OGTT test showed hyperinsulinemia, dyslipidemia, glycosylated hemoglobin 12.3%. Abdominal CT showed fatty liver and small right kidney. Cranial MRI showed that bilateral cerebral hemispheres, cerebellum, and brainstem were small in size, and the front of the falx was widened. Whole-exon gene detection revealed 2 novel heterozygous mutations in CDK5RAP2 gene: c.4270G>T (P.E1424X), c.1594C>T (P.Q532X), and 1 novel splicing mutation in HNF1B: c.1534+10C>T. The three mutations in this case were all novel mutations.

Conclusion: This patient with MODY5 and MCPH type 3, the connection between the two has not been reported. What’s more, we found 3 novel mutations, which expands the database of HNF1B and CDK5RAP2 gene mutations.