Atypical presentation of Charcot-Marie-Tooth disease type 2Q by mutations on DHTKD1 and NTRK2 genes

Abstract

Background: Charcot-Marie-Tooth disease type 2Q (CMT2Q) is a rare disorder (< 1/1,000,000 individuals worldwide) linked to chromosome 10p14 in the DHTKD1 gene. This phenotype is characterized by an adolescent or adulthood-onset, slowly progressive distal muscle weakness and symmetrical atrophy associated with reduced or absent deep tendon reflexes. Currently, only two familiar cases from China have been reported: one familiar case of eight individuals affected by isolated DHTKD1 gene mutation and one familiar case of two individuals affected by DHTKD1 gene mutation and GJB1 gene mutation. Case report: We present the case of a 10-year-old male patient with obesity, frequent falls, swollen legs and thighs, and pain in the lower and upper limbs. We performed the clinical evaluation and a clinical targeted exome test, which reported mutations on DHTKD1 y NTRK2 genes. Conclusions: Due to scientific and technological advances, genetic dysfunctions that can cause different diseases have been identified with greater sensitivity. Globally, this is the eleventh case reported of DHTKD1 gene mutation linked to CMT2Q. Moreover, this is the first case related to NTRK2 gene mutation (linked to obesity, hyperphagia, and delayed development). The patient showed an atypical CMT2Q phenotype additional to obesity. Therefore, we propose to study metabolic disorders linked to hereditary peripheral neuropathies.

The Pleiotropic Potential of BDNF beyond Neurons: Implication for a Healthy Mind in a Healthy Body

“…A rare de novo missense variant in BDNF and seven NTRK2 mutations along with three variants previously reported [23] have also been functionally characterized by Sonoyama et al Clinical data collected from carriers of BDNF/TrkB variants showed in addition to severe obesity, a spectrum of neurobehavioral disorders such as hyperactivity, learning deficit and shot-term memory impairment [29]. Interestingly, a latest study reports an atypical Charcot-Marie-Tooth disease type 2Q phenotype with obesity likely related to the mutation identified in the coding region of the NTRK2 gene [30].…”

The Pleiotropic Potential of BDNF beyond Neurons: Implication for a Healthy Mind in a Healthy Body

“…A rare de novo missense variant in BDNF and seven NTRK2 mutations along with three variants previously reported [38] have also been functionally characterized by Sonoyama et al Clinical data collected from carriers of BDNF/TrkB variants showed in addition to severe obesity, a spectrum of neurobehavioral disorders such as hyperactivity, learning deficit and shot-term memory impairment [44]. www.videleaf.com Interestingly, a latest study reports an atypical Charcot-Marie-Tooth disease type 2Q phenotype with obesity likely related to the mutation identified in the coding region of the NTRK2 gene [45] All things considered, there is clear evidence of the crucial role of BDNF in modulating body weight and energy homeostasis, although further studies are needed to better elucidate the BDNF involvement in these syndromes.…”

Administration of Phosphonate Inhibitors of Dehydrogenases of 2-Oxoglutarate and 2-Oxoadipate to Rats Elicits Target-Specific Metabolic and Physiological Responses

“…Although both OADH and OGDH catalyze oxidative decarboxylation of 2-oxoadipate, the function of OADH is not redundant. Hereditary dysfunctions of OADH cause disease states, such as impaired insulin sensitivity ( Xu et al, 2018 ; Xu et al, 2019 ) or Charcot–Marie-Tooth disease ( Xu et al, 2012 ; Xu et al, 2018 ; Luan et al, 2020 ; Castro-Coyotl et al, 2021 ; Yalcintepe et al, 2021 ). Large-scale genome association studies reveal that common variants of the human DHTKD1 gene may cause type 2 diabetes and cardiovascular problems ( Wu et al, 2014 ; Plubell et al, 2018 ; Timmons et al, 2018 ; Wang et al, 2021 ).…”