Postnatal Microcephaly and Pain Insensitivity Due to a De Novo Heterozygous DNM1L Mutation Causing Impaired Mitochondrial Fission and Function

作者：Sheffer Ruth; Douiev Liza; Edvardson Simon; Shaag Avraham; Tamimi Khaled; Soiferman Devorah; Meiner Vardiella; Saada Ann^*

来源：American Journal of Medical Genetics, Part A, 2016, 170(6): 1603-1607.

DOI：10.1002/ajmg.a.37624

• mitochondrial fission
• mitochondrial respiratory chain
• mitochondrial dynamics
• mitochondrial disease
• dynamin-related protein 1
• DRP1
• DNM1L gene
• postnatal microcephaly
• pain insensitivity

An emerging class of mitochondrial disorders is caused by mutations in nuclear genes affecting mitochondrial dynamics and function. One of these is the DNM1L gene encoding the dynamin-related protein 1 (DRP1), which is pivotal in the mitochondrial fission process. Here, we describe a patient with a novel dominant-negative, de novo DNM1L mutation, which expands the clinical spectrum. The patient reported here exhibits a chronic neurological disorder, characterized by postnatal microcephaly, developmental delay, and pain insensitivity. Muscle biopsy disclosed decreased respiratory chain complex IV activity. Exome sequencing showed a de novo heterozygous c.1084G>A (p.G362S) mutation. Subsequent studies of patient skin fibroblasts showed markedly impaired mitochondrial fission and a partial respiratory chain defect while peroxisomal morphology remained intact. Human foreskin fibroblasts over-expressing the mutant DNM1L gene displayed aberrant mitochondrial morphology.

• 出版日期2016-6