Ching-Wan Lam1, Wai-Lan Yeung2, Tsz-Ki Ling3, Ka-Chung Wong3, Chun-Yiu Law3. 1. Department of Pathology, Queen Mary Hospital, Hong Kong, China; Department of Pathology, The University of Hong Kong, Hong Kong, China. Electronic address: ching-wanlam@pathology.hku.hk. 2. Department of Paediatrics, Hong Kong Children Hospital, Hong Kong, China. 3. Department of Pathology, Queen Mary Hospital, Hong Kong, China.
Abstract
BACKGROUND: Mitochondrial DNA depletion syndrome is a group of heterogeneous diseases with non-specific presentation. The common feature is the quantitative depletion of mitochondrial DNA without qualitative defects. Diagnosis of these diseases poses a challenge and whole exome sequencing is often needed for their diagnoses. CASE: Two siblings of a quartet family, presenting with hypotonia, microcephaly and severe intellectual disability, have been diagnosed to harbor two heterozygous variants in trans in the DTYMK gene of the thymidine biosynthesis pathway. Mitochondrial DNA depletion has been demonstrated in silico in the more severe sibling. CONCLUSIONS: We suggest the consideration of incorporating DTYMK as one of the associated genes of mitochondrial DNA depletion syndrome (MDDS). DTYMK may be the missing link in the mitochondrial nucleotide salvage pathway but further characterization and additional evidence would be needed.
BACKGROUND: Mitochondrial DNA depletion syndrome is a group of heterogeneous diseases with non-specific presentation. The common feature is the quantitative depletion of mitochondrial DNA without qualitative defects. Diagnosis of these diseases poses a challenge and whole exome sequencing is often needed for their diagnoses. CASE: Two siblings of a quartet family, presenting with hypotonia, microcephaly and severe intellectual disability, have been diagnosed to harbor two heterozygous variants in trans in the DTYMK gene of the thymidine biosynthesis pathway. Mitochondrial DNA depletion has been demonstrated in silico in the more severe sibling. CONCLUSIONS: We suggest the consideration of incorporating DTYMK as one of the associated genes of mitochondrial DNA depletion syndrome (MDDS). DTYMK may be the missing link in the mitochondrial nucleotide salvage pathway but further characterization and additional evidence would be needed.
Authors: Jo M Vanoevelen; Jörgen Bierau; Janine C Grashorn; Ellen Lambrichs; Erik-Jan Kamsteeg; Levinus A Bok; Ron A Wevers; Marjo S van der Knaap; Marianna Bugiani; Junmei Hu Frisk; Rita Colnaghi; Mark O'Driscoll; Debby M E I Hellebrekers; Richard Rodenburg; Carlos R Ferreira; Han G Brunner; Arthur van den Wijngaard; Ghada M H Abdel-Salam; Liya Wang; Constance T R M Stumpel Journal: Acta Neuropathol Date: 2021-12-17 Impact factor: 17.088