Biallelic Ndufa13 Variants Lead to a Neurodevelopmental Phenotype With Gradual Neurological Impairment

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Biallelic Ndufa13 Variants Lead to a Neurodevelopmental Phenotype With Gradual Neurological Impairment Publisher

Kaiyrzhanov R^{1, 2} ; Thompson K³ ; Efthymiou S¹ ; Mukushev A⁴ ; Zharylkassyn A⁵ ; Prasad C⁶ ; Karimiani EG^{1, 7} ; Alvi JR⁸ ; Niyazov D⁹ ; Alahmad A¹⁰ ; Babaei M¹¹ ; Tajsharghi H¹² ; Albash B¹³ ; Alaqeel A¹³ Show All Authors

Kaiyrzhanov R^{1, 2}
Thompson K³
Efthymiou S¹
Mukushev A⁴
Zharylkassyn A⁵
Prasad C⁶
Karimiani EG^{1, 7}
Alvi JR⁸
Niyazov D⁹
Alahmad A¹⁰
Babaei M¹¹
Tajsharghi H¹²
Albash B¹³
Alaqeel A¹³
Charif M^{14, 15, 16}
Hashemi N¹⁷
Heidari M¹⁸
Kalantar SM¹⁹
Lenaers G^{20, 21}
Mehrjardi MYV²²
Srinivasan VM²³
Gowda VK²³
Mirabutalebi SH¹⁹
Carere DA²⁴
Movahedinia M²⁵
Murphy D²⁶
Mcfarland R^{3, 27}
Abdelhamid MS²⁸
Elhossini RM²⁹
Alavi S¹
Napier M²⁴
Belangerquintana A³⁰
Prasad AN³¹
Jakobczyk J⁶
Roubertie A³²
Rupar T^{33, 34}
Sultan T⁸
Toosi MB^{17, 35}
Sazanov L³⁶
Severino M³⁷
Houlden H¹
Taylor RW^{3, 27}
Maroofian R¹

Source: Brain Communications Published:2025

Abstract

Biallelic variants in NADH (nicotinamide adenine dinucleotide (NAD) + hydrogen (H))-ubiquinone oxidoreductase 1 alpha subcomplex 13 have been linked to mitochondrial complex I deficiency, nuclear type 28, based on three affected individuals from two families. With only two families reported, the clinical and molecular spectrum of NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13–related diseases remains unclear. We report 10 additional affected individuals from nine independent families, identifying four missense variants (including recurrent c.170G > A) and three ultra-rare or novel predicted loss-of-function biallelic variants. Updated clinical–radiological data from previously reported families and a literature review compiling clinical features of all reported patients with isolated complex I deficiency caused by 43 genes encoding complex I subunits and assembly factors are also provided. Our cohort (mean age 7.8 ± 5.4 years; range 2.5–18) predominantly presented a moderate-to-severe neurodevelopmental syndrome with oculomotor abnormalities (84%), spasticity/hypertonia (83%), hypotonia (69%), cerebellar ataxia (66%), movement disorders (58%) and epilepsy (46%). Neuroimaging revealed bilateral symmetric T2 hyperintense substantia nigra lesions (91.6%) and optic nerve atrophy (66.6%). Protein modeling suggests missense variants destabilize a critical junction between the hydrophilic and membrane arms of complex I. Fibroblasts from two patients showed reduced complex I activity and compensatory complex IV activity increase. This study characterizes NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13–related disease in 13 individuals, highlighting genotype–phenotype correlations. © The Author(s) 2024.

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Style	Citing Format
MLA	Kaiyrzhanov R, et al.. "Biallelic Ndufa13 Variants Lead to a Neurodevelopmental Phenotype With Gradual Neurological Impairment." Brain Communications, vol. 7, no. 1, 2025, pp. -.
APA	Kaiyrzhanov R, Thompson K, Efthymiou S, Mukushev A, Zharylkassyn A, Prasad C, Karimiani EG, Alvi JR, Niyazov D, Alahmad A, Babaei M, Tajsharghi H, Albash B, Alaqeel A, Charif M, Hashemi N, Heidari M, Kalantar SM, Lenaers G, ... Maroofian R (2025). Biallelic Ndufa13 Variants Lead to a Neurodevelopmental Phenotype With Gradual Neurological Impairment. Brain Communications, 7(1), -.
Chicago	Kaiyrzhanov R, Thompson K, Efthymiou S, Mukushev A, Zharylkassyn A, Prasad C, Karimiani EG, et al.. "Biallelic Ndufa13 Variants Lead to a Neurodevelopmental Phenotype With Gradual Neurological Impairment." Brain Communications 7, no. 1 (2025): -.
Harvard	Kaiyrzhanov R et al. (2025) 'Biallelic Ndufa13 Variants Lead to a Neurodevelopmental Phenotype With Gradual Neurological Impairment', Brain Communications, 7(1), pp. -.
Vancouver	Kaiyrzhanov R, Thompson K, Efthymiou S, Mukushev A, Zharylkassyn A, Prasad C, et al.. Biallelic Ndufa13 Variants Lead to a Neurodevelopmental Phenotype With Gradual Neurological Impairment. Brain Communications. 2025;7(1):-.
BibTex	@article{ author = {Kaiyrzhanov R and Thompson K and Efthymiou S and Mukushev A and Zharylkassyn A and Prasad C and Karimiani EG and Alvi JR and Niyazov D and Alahmad A and Babaei M and Tajsharghi H and Albash B and Alaqeel A and Charif M and Hashemi N and Heidari M and Kalantar SM and Lenaers G and Mehrjardi MYV and Srinivasan VM and Gowda VK and Mirabutalebi SH and Carere DA and Movahedinia M and Murphy D and Mcfarland R and Abdelhamid MS and Elhossini RM and Alavi S and Napier M and Belangerquintana A and Prasad AN and Jakobczyk J and Roubertie A and Rupar T and Sultan T and Toosi MB and Sazanov L and Severino M and Houlden H and Taylor RW and Maroofian R}, title = {Biallelic Ndufa13 Variants Lead to a Neurodevelopmental Phenotype With Gradual Neurological Impairment}, journal = {Brain Communications}, volume = {7}, number = {1}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Kaiyrzhanov R AU - Thompson K AU - Efthymiou S AU - Mukushev A AU - Zharylkassyn A AU - Prasad C AU - Karimiani EG AU - Alvi JR AU - Niyazov D AU - Alahmad A AU - Babaei M AU - Tajsharghi H AU - Albash B AU - Alaqeel A AU - Charif M AU - Hashemi N AU - Heidari M AU - Kalantar SM AU - Lenaers G AU - Mehrjardi MYV AU - Srinivasan VM AU - Gowda VK AU - Mirabutalebi SH AU - Carere DA AU - Movahedinia M AU - Murphy D AU - Mcfarland R AU - Abdelhamid MS AU - Elhossini RM AU - Alavi S AU - Napier M AU - Belangerquintana A AU - Prasad AN AU - Jakobczyk J AU - Roubertie A AU - Rupar T AU - Sultan T AU - Toosi MB AU - Sazanov L AU - Severino M AU - Houlden H AU - Taylor RW AU - Maroofian R TI - Biallelic Ndufa13 Variants Lead to a Neurodevelopmental Phenotype With Gradual Neurological Impairment JO - Brain Communications VL - 7 IS - 1 SP - EP - PY - 2025 ER -