Ask about this productRelated genes to: GDAP1 antibody
- Gene:
- GDAP1 NIH gene
- Name:
- ganglioside induced differentiation associated protein 1
- Previous symbol:
- CMT4A
- Synonyms:
- CMT4, CMT2K
- Chromosome:
- 8q21.11
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-25
- Date modifiied:
- 2019-04-23
Related products to: GDAP1 antibody
Related articles to: GDAP1 antibody
- Charcot-Marie-Tooth (CMT) disease comprises a genetically diverse range of disorders affecting the peripheral nervous system. We report an axonal CMT (CMT 2) case from India with a novel heterozygous variant of uncertain significance detected in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene. A 12-year-old male patient presented with severe distal lower limb weakness (bilateral foot drop) progressing proximally. Bilateral pes-cavus, high-steppage gait, reduced power in bilateral lower limbs, bilaterally absent ankle jerks, and no cerebellar or pyramidal signs/vocal cord paresis were salient clinical findings that suggested the clinical diagnosis of Hereditary motor and sensory neuropathy (HMSN)/CMT disease. Neurophysiological tests revealed axonal CMT. Genetic studies showed a novel heterozygous missense variant classified as a variant of uncertain significance in the GDAP1 gene. Although the causative role of the variant remained unclear, mutation in the GDAP1 gene, clinical features, and characteristic electrophysiological findings exhibiting axonal CMT supported the subtype diagnosis as probable CMT type 2K in the patient. The present report emphasizes the significance of clinical and neurophysiological findings in CMT when analyzing sequencing data in the era of next-generation sequencing, particularly when variant of uncertain significance are found. - Source: PubMed
Publication date: 2026/05/06
Gupta SangeetaRukadikar Charushila Atul - BACKGROUND: Charcot–Marie–Tooth disease and related neuropathies (CMTR) are heterogeneous inherited neuropathies with variable progression, yet data on pediatric disease progression by neurophysiological subtype are limited. We evaluated 1-year clinical and functional changes in children with CMTR and compared axonal versus demyelinating trajectories. METHODS: We conducted a prospective cohort study of 20 Thai children with CMTR who were aged 3–20 years. Participants were assessed at baseline and after 1 year using the Rasch-modified Charcot–Marie–Tooth Examination Score (CMTES-R), Charcot–Marie–Tooth Pediatric Scale (CMTPedS), manual muscle testing (MMT), Foot Posture Index, and muscle length testing. Within-subject changes in clinical outcomes over time were assessed using appropriate paired statistical tests. RESULTS: Thirteen patients had axonal forms and seven had demyelinating forms; the patients’ mean age was 13.0 ± 4.9 years. The axonal variants involved MFN2 (n = 3), GDAP1 (n = 2), and GAN, GJB1, IGHMBP2, KIF1A, PRDM12 (n = 1 each); 3 axonal variants were genetically undiagnosed. The demyelinating variants comprised MPZ (n = 2), PMP22 duplication (n = 2), EGR2 (n = 1), NEFL (n = 1), and PMP22 deletion (n = 1). At both time points, 85% of the patients were ambulatory, 15% used a wheelchair, and 65% used an ankle-foot orthosis. CMTPedS increased by 1.0 ± 3.4 points over 1 year (p = 0.271), with a larger change in axonal versus demyelinating cases (+ 1.1 ± 3.2 vs. + 0.7 ± 4.0). CMTES-R changed minimally (median + 0.5), and MMT showed stable strength. CONCLUSION: The clinical progression in pediatric CMTR was heterogeneous and differed by neurophysiological subtype, with more pronounced 1-year functional decline in axonal disease. These findings support vigilant longitudinal monitoring of pediatric CMTR, particularly where genetic testing access is limited. - Source: PubMed
Publication date: 2026/04/21
Inmongkol ChonladaVorasan NutchavadeeLimpaninlachat SivapornSereephaowong NiramonKulsirichawaroj PimchanokSanmaneechai OraneeBurns Joshua - Sheep production contributes to a secure and diverse food and fibre supply in the United States, with growing ethnic diversity strengthening demand. Katahdin is a composite hair-type sheep breed developed in the United States that has become the most popular breed in many regions of the country and the first one to have genomic selection implemented in its breeding program. Therefore, the main objectives of this study were to estimate variance components of reproductive traits, including number of lambs born (NLB), number of lambs weaned (NLW), age at first lambing (AFL), and interval from first to second lambing (LI), in Katahdin sheep using the AIREML method and the single-step Genomic Best Linear Unbiased Prediction (ssGBLUP) approach, and to identify genomic regions and candidate genes associated with these traits. The datasets used consisted of 127,536 animals in the pedigree, phenotypic records of 56,128 parities from 24,067 ewes, and genomic data from 10,032 animals with 30,308 single-nucleotide polymorphisms (SNP) after quality control. Analyses were performed using the BLUPF90 family of programs. We observed low heritability estimates for all studied traits (0.09 ± 0.00 for NLB, 0.08 ± 0.00 for NLW, 0.09 ± 0.01 for AFL, and 0.08 ± 0.01 for LI). The genetic correlations between the traits ranged from 0.17 ± 0.02 (AFL and LI) to 0.79 ± 0.02 (NLB and NLW). All traits were found to be highly polygenic with all 14 significant SNP on eight (OAR) chromosomes (3, 6, 7, 8, 9, 12, 13, and 15) having small effects on the total variability on the traits. These SNP were located near or within 18 candidate genes: four genes associated with NLB (AAK1, GFPT1, SLC23A2, and GDAP1), four with NLW (ARHGAP18, TTLL2, UNC93A, and GPR31), six with AFL (NAP1L5, FAM13A, HS3ST1, CCDC181, NME7, and BLZF1), and four with LI (TAF4, CDH4, CADM1, and SEL1L). These candidate genes have been previously associated with fertility, embryonic development, growth, disease resistance, and climatic adaptation traits. Our findings indicate that fertility and reproduction traits in Katahdin sheep can be improved through direct genetic selection. Genetic improvement for these traits will benefit from genomic selection as more accurate estimates of breeding values for selection candidates can be obtained at a younger age. Although the studied traits are influenced by a complex interplay of genetic and environmental factors, the candidate genes identified enabled a better understanding of the biological mechanisms underlying reproductive performance in Katahdin sheep. - Source: PubMed
Publication date: 2026/03/30
Ospina Alejandra ToroLewis Ronald MFreking Bradley ABurke Joan MMurphy Thomas WWilson Carrie SBrito Luiz F - The mitochondrial outer membrane (OMM) plays a crucial role in maintaining cellular homeostasis by regulating mitochondrial dynamics, organelle interactions, and stress responses. In peripheral neurons-cells with high metabolic demands and long axons-the OMM acts as a vital platform for coordinating bioenergetics, calcium signaling, and redox balance. Ganglioside-induced differentiation-associated protein 1 (GDAP1), an OMM-anchored protein, has emerged as a key regulator of mitochondrial fission and transport, redox homeostasis, and mitochondrial membrane contact sites (MCSs). Genetic variants in GDAP1 cause Charcot-Marie-Tooth disease (CMT), emphasizing its essential role in peripheral nerve function. This review highlights the multifaceted functions of GDAP1 in neuronal physiology and as a model protein that integrates organelle communication and mitochondrial biology. We further discuss how GDAP1 dysfunction leads to structural and functional impairments in peripheral neurons, proposing the OMM and its microenvironment as critical targets for therapeutic intervention in inherited neuropathies. - Source: PubMed
Publication date: 2026/02/10
Cantarero LaraHoenicka JanetPalau Francesc - Autosomal recessive ataxia is characterized primarily by gait and balance problems. Peripheral neuropathy, which affects peripheral nervous system is manifested as sensory loss, pain, numbness and/or burning sensation accompanied by distal muscle atrophy which can cause limb deformities. We recruited seven consanguineous families having symptoms of peripheral neuropathy or ataxia for the identification of possible genetic defects underlying their disease conditions. Exome sequencing was completed for multiple participants of each family and data were filtered to retain rare deleterious variants. We identified disease-causing variants for five out of seven families. Different variants of GDAP1 were delineated in members of two families; while those of AFG3L2, MFSD8 and SETX affected members in one family each. Interestingly, one patient was homozygous for both a GDAP1 and a pathogenic MMACHC variant. Genetic heterogeneity was observed in one family since a homozygous frameshift variant of ALS2 was found in a patient while it was absent in his two affected first cousins. No genetic cause was identified for these two patients and those in another family. Hence, exome sequencing pinpointed molecular causes of recessively inherited ataxia or peripheral neuropathy in five participating families. This research has broadened the clinical spectrum of some of these genetic disorders. - Source: PubMed
Publication date: 2026/01/28
Aslam FaizaWajid MuhammadButt Amina IftikharWohler ElizabethSeo Go HunJi WeizhenLakhani Saquib ASobreira NaraNaz Sadaf