Eman Bakhsh | King Saud University (original) (raw)

Papers by Eman Bakhsh

Journal of Medical Genetics, 2005

Neurosciences (Riyadh, Saudi Arabia), Apr 1, 2002

The Journal of medical research, 2017

The Journal of medical research, 2017

Cowden syndrome is a rare autosomal-dominant disease characterized by multisystem hamartomas usua... more Cowden syndrome is a rare autosomal-dominant disease characterized by multisystem hamartomas usually affecting the skin, thyroid gland, breast, and gastrointestinal tract; these hamartomastend to undergo malignant transformation in various tissues. We describe a 32-year-old woman who presented with a progressive headache, neck pain, nausea, vomiting, transient loss of vision, dizziness, and unsteady gait during the previous2 months; she had one episode of a seizure and a previous history of an ovarian cyst manifesting as abnormal menses. Brain magnetic resonance imaging (MRI) revealed a left cerebellar mass with features suggestive of dysplastic gangliocytoma with obstructive hydrocephalus in addition to multiple meningiomas. Imaging features raised the suspicion of Cowden syndrome (CS). Thus, the patient underwent suboccipital craniotomy for resection of the left cerebellar mass; pathological and immunohistochemical examination confirmed the diagnosis of CS. Most cases found in the...

JCO Precision Oncology, 2020

Author affiliations and support information (if applicable) appear at the end of this article.

Neuro-Oncology, 2020

PURPOSE In this case report, we document new recommendations for the treatment of pediatric gliob... more PURPOSE In this case report, we document new recommendations for the treatment of pediatric glioblastoma based on a genetic understanding of the disease. PATIENTS AND METHODS A Saudi girl aged 18 months presented with a history of right sided weakness and partial seizures. MRI revealed the presence of large complex left frontal tumor. Craniotomy and gross total resection were performed. post-operatively The patient showed excellent recovery with no neurological deficits. Pathology reports confirmed glioblastoma (GBM). Due to the expected poor survival, the patient’s family declined standard therapy, including chemotherapy and/or radiation therapy. RESULTS Molecular analysis showed positive fusion mutations for ETV6-NTRK3 making the patient an ideal candidate for larotrectinib, an oral tyrosine kinase (TRK) inhibitor. Unfortunately, follow-up MRI showed local tumor recurrence at 3-months post-surgery. The family agreed to the initiation of oral larotrectinib as a less invasive therap...

American Journal of Case Reports, 2018

Rare disease Background: Epidural venous plexus (EVP) engorgement occurs due to many conditions, ... more Rare disease Background: Epidural venous plexus (EVP) engorgement occurs due to many conditions, so it can be easily misdiagnosed. This becomes problematic when the diagnosis requires prompt treatment for a good outcome, especially when it results in cauda equina syndrome (CES). We report a case of extensive iliocaval thrombosis leading to epidural venous plexus and ascending lumbar vein engorgement as an outcome of deep venous thrombosis (DVT) due to probable adverse effects of oral combined contraceptive pills (OCCP). Case Report: A 42-year-old woman presented to a rural medical facility with bilateral lower-limb swelling and skin darkening for 2 days. She was transferred to a tertiary medical facility where her condition deteriorated to severe CES. A lower-limbs ultrasonography confirmed the presence of extensive DVT extending to the lower segment of the inferior vena cava. Spine magnetic resonance imaging showed abnormal enhancement of the conus medullaris with thick enhanced cauda equina nerve roots, consistent with a possible case of Guillain-Barré syndrome. However, there was engorgement of the EVP extending to the ascending lumbar, azygos, and hemiazygos veins, which was misdiagnosed. The patient was managed immediately with low-molecular-weight heparin and steroids. She died 4 weeks after admission due to hospital-acquired pneumonia and acute respiratory distress syndrome, probably due to the high dose of steroids. Conclusions: Acute CES has a wide differential diagnosis. This report describes an unusual cause of CES and emphasizes the importance of early recognition to avoid misdiagnosis and management delay. Early identification of this clinical entity markedly decreases morbidity and mortality and thus improves the prognosis. Likewise, underlying causing factors such as venous congestion due to OCCP-related DVT should be considered in the diagnosis.

Case Reports in Neurological Medicine, 2017

Polyostotic sclerosing histiocytosis, also known as Erdheim-Chester disease (ECD), is a rare form... more Polyostotic sclerosing histiocytosis, also known as Erdheim-Chester disease (ECD), is a rare form of non-Langerhans histiocytosis. ECD has wide clinical spectrums which mainly affect skeletal, neurological, dermatological, retroperitoneal, cardiac, and pulmonary manifestations. Here we describe a case of ECD in a 45-year-old female who presented initially with bilateral knee pain and homonymous superior quadrantanopia progressed to ophthalmoplegia and complete visual loss of the left eye over a period of one year. Plain X-ray of both knees showed bilateral patchy sclerosis of the distal femur and upper parts of the tibiae. Initial brain magnetic resonance imaging (MRI) showed bilateral enhancing masses in the temporal lobes anterior to the temporal horns, thickening of the pituitary stalk, partially empty sella, and involvement of the left cavernous sinus one year later. Our case is a peculiar case of ECD initially presented with unilateral homonymous superior quadrantanopia due to ...

Annals of Saudi Medicine, 1996

Saudi Medical Journal, Oct 1, 2006

In this report, we describe a patient with left conjugate gaze palsy and internuclear ophthalmopl... more In this report, we describe a patient with left conjugate gaze palsy and internuclear ophthalmoplegia on the opposite gaze one-and-a-half-syndrome [11/2 syndrome]. Magnetic resonance imaging of the brain showed nodular enhancing brain stem lesions. After excluding other potential diseases, tuberculoma was thought to be the underlying etiology. Recovery was achieved 8 weeks after initiation of anti-tuberculous anti-TB therapy. The isolated nature of the tuberculoma and the association with this rare syndrome is highlighted.

Neurosciences (Riyadh, Saudi Arabia), 2000

The association between acute rise of blood pressure and encephalopathy with early recognition, a... more The association between acute rise of blood pressure and encephalopathy with early recognition, and therapy reversibility has been reported. We reported a case of a young lady in postnatal period, presented with acute rise of blood pressure, encephalopathy, quadriparesis, and apraxia. Magnetic resonance imaging of the brain showed hyperintense lesions in occipital, parietal and right temporal areas. Cerebral angio showed multiple segmental vasoconstriction and narrowing of intracerebral vessels. Immediate control of blood pressure enhanced recovery but it is incomplete.

Neurosciences (Riyadh, Saudi Arabia), 2002

Neuromyelitis optica disease is characterized by simultaneous or successive attacks involving bot... more Neuromyelitis optica disease is characterized by simultaneous or successive attacks involving both the optics nerves and spinal cord without any evidence of the disease elsewhere. We report a 22-year-old Saudi woman with relapsing neuromyelitis optica disease. She had all the clinical, cerebrospinal fluid, and radiological features that differ from primary demyelinating disease. However, our patient responded well to long-term corticosteroid therapy and azathioprine with improvement in her expanded disability status scale, and ambulation. In addition, no acute relapses occurred with significant improvement on magnetic resonance imaging lesions and favorable outcome.

Neurosurgery Rounds: Questions and Answers, 2011

Neurology, 2006

Pelizaeus-Merzbacher-like disease (PMLD) is an inherited hypomyelinating leukoencephalopathy with... more Pelizaeus-Merzbacher-like disease (PMLD) is an inherited hypomyelinating leukoencephalopathy with onset in early infancy. Like Pelizaeus-Merzbacher disease (PMD), PMLD is characterized clinically by nystagmus, cerebellar ataxia, and spasticity, due to a permanent lack of myelin deposition in the brain. Mutations in the GJA12 gene, encoding connexin 47 (Cx47), were recently reported in five children with autosomal recessive PMLD. To evaluate the impact of mutations in the GJA12 gene in, and define the clinical and neuroimaging features of, autosomal recessive PMLD. The authors screened for GJA12 mutations in 10 additional PMLD families originating from Italy, Pakistan, and Saudi Arabia. Three novel homozygous GJA12 mutations were identified in 12 mutant cases distributed in 3 of 10 families. The mutations segregated with the disease according to an autosomal recessive trait and included one missense (G236S) and two nonsense (L281fs285X and P131fs144X) changes. The identification of homozygous mutations predicting the synthesis of aberrant and truncated polypeptides, and their tight segregation with the disease in very large families, clearly demonstrate that the loss of Cx47 function is the cause of the disease. The phenotype of GJA12-related Pelizaeus-Merzbacher-like disease is fairly homogeneous and similar to that of Pelizaeus-Merzbacher disease. However, slower progression of symptoms, greater preservation of cognitive functions, and partial myelination of corticospinal tracts at MRI were distinctive features, which could help in the differential diagnosis.

The Journal of Pediatrics, 2014

Objective To determine the frequency of mitochondrial DNA depletion syndrome (MDS) in infants wit... more Objective To determine the frequency of mitochondrial DNA depletion syndrome (MDS) in infants with cholestasis and liver failure and to further clarify the clinical, biochemical, radiologic, histopathologic, and molecular features associated with MDS due to deoxyguanosine kinase (DGUOK) and MPV17 gene mutations. Study design We studied 20 infants with suspected hepatocerebral MDS referred to our tertiary care center between 2007 and 2013. Genomic DNA was isolated from blood leukocytes, liver, and/or skeletal muscle samples by standard methods. Mitochondrial DNA copy number relative to nuclear DNA levels was determined in muscle and/ or liver DNA using real-time quantitative polymerase chain reaction and compared with age-matched controls. Nuclear candidate genes, including polymerase g, MPV17, and DGUOK were sequenced using standard analyses. Results We identified pathogenic MPV17 and DGUOK mutations in 11 infants (6 females) representing 2.5% of the 450 cases of infantile cholestasis and 22% of the 50 cases of infantile liver failure referred to our center during the study period. All of the 11 patients manifested cholestasis that was followed by a rapidly progressive liver failure and death before 2 years of life. Mitochondrial DNA depletion was demonstrated in liver or muscle for 8 out of the 11 cases where tissue was available. Seven patients had mutations in the MPV17 gene (3 novel mutations), 4 patients had DGUOK mutations (of which 2 were novel mutations). Conclusion Mutations in the MPV17 and DGUOK genes are present in a significant percentage of infants with liver failure and are associated with poor prognosis.

Head & Neck Oncology, 2011

Fibrous dysplasia (FD) and aneurysmal bone cyst (ABC) are uncommon benign intraosseous lesions. S... more Fibrous dysplasia (FD) and aneurysmal bone cyst (ABC) are uncommon benign intraosseous lesions. Simultaneous occurrence of both lesions is extremely rare. We present an example of concomitant FD and ABC in a 7 year-old with left eye blindness and discharge of one month duration. Physical examination revealed a proptotic left eye and bulging of the hard palate. CT and MRI are consistent with FD and ABC that involved the sphenoid and ethmoidal bones bilaterally. Incomplete combined endonasalcranial resection was performed. The patient presented five months postoperatively with a large recurrence and subsequent follow up was lost. Concomitant FD with ABC may occur in paranasal sinuses and may develop rapidly and exhibit locally aggressive behavior.

Annals of Saudi Medicine, 1996

Case reports in pediatrics, 2017

Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy ... more Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing's sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT) imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) seeding from the L5 to the S4 vertebrae. Primary cranial Ewing's sarcoma is considered ...

American Journal of Human Genetics, 2008

Cytochrome c oxidase (COX) deficiency, one of the most common respiratory-chain defects in humans... more Cytochrome c oxidase (COX) deficiency, one of the most common respiratory-chain defects in humans, has been associated with mutations in either mitochondrial DNA genes or nucleus-encoded proteins that are not part in but promote the biogenesis of COX. Mutations of nucleus-encoded structural subunits were sought for but never found in COX-defective patients, leading to the conjecture that they may be incompatible with extra-uterine survival. We report a disease-associated mutation in one such subunit, COX6B1. Nuclear-encoded COX genes should be reconsidered and included in the diagnostic mutational screening of human disorders related to COX deficiency.

Journal of Medical Genetics, 2005

Neurosciences (Riyadh, Saudi Arabia), Apr 1, 2002

The Journal of medical research, 2017

The Journal of medical research, 2017

Cowden syndrome is a rare autosomal-dominant disease characterized by multisystem hamartomas usua... more Cowden syndrome is a rare autosomal-dominant disease characterized by multisystem hamartomas usually affecting the skin, thyroid gland, breast, and gastrointestinal tract; these hamartomastend to undergo malignant transformation in various tissues. We describe a 32-year-old woman who presented with a progressive headache, neck pain, nausea, vomiting, transient loss of vision, dizziness, and unsteady gait during the previous2 months; she had one episode of a seizure and a previous history of an ovarian cyst manifesting as abnormal menses. Brain magnetic resonance imaging (MRI) revealed a left cerebellar mass with features suggestive of dysplastic gangliocytoma with obstructive hydrocephalus in addition to multiple meningiomas. Imaging features raised the suspicion of Cowden syndrome (CS). Thus, the patient underwent suboccipital craniotomy for resection of the left cerebellar mass; pathological and immunohistochemical examination confirmed the diagnosis of CS. Most cases found in the...

JCO Precision Oncology, 2020

Author affiliations and support information (if applicable) appear at the end of this article.

Neuro-Oncology, 2020

PURPOSE In this case report, we document new recommendations for the treatment of pediatric gliob... more PURPOSE In this case report, we document new recommendations for the treatment of pediatric glioblastoma based on a genetic understanding of the disease. PATIENTS AND METHODS A Saudi girl aged 18 months presented with a history of right sided weakness and partial seizures. MRI revealed the presence of large complex left frontal tumor. Craniotomy and gross total resection were performed. post-operatively The patient showed excellent recovery with no neurological deficits. Pathology reports confirmed glioblastoma (GBM). Due to the expected poor survival, the patient’s family declined standard therapy, including chemotherapy and/or radiation therapy. RESULTS Molecular analysis showed positive fusion mutations for ETV6-NTRK3 making the patient an ideal candidate for larotrectinib, an oral tyrosine kinase (TRK) inhibitor. Unfortunately, follow-up MRI showed local tumor recurrence at 3-months post-surgery. The family agreed to the initiation of oral larotrectinib as a less invasive therap...

American Journal of Case Reports, 2018

Rare disease Background: Epidural venous plexus (EVP) engorgement occurs due to many conditions, ... more Rare disease Background: Epidural venous plexus (EVP) engorgement occurs due to many conditions, so it can be easily misdiagnosed. This becomes problematic when the diagnosis requires prompt treatment for a good outcome, especially when it results in cauda equina syndrome (CES). We report a case of extensive iliocaval thrombosis leading to epidural venous plexus and ascending lumbar vein engorgement as an outcome of deep venous thrombosis (DVT) due to probable adverse effects of oral combined contraceptive pills (OCCP). Case Report: A 42-year-old woman presented to a rural medical facility with bilateral lower-limb swelling and skin darkening for 2 days. She was transferred to a tertiary medical facility where her condition deteriorated to severe CES. A lower-limbs ultrasonography confirmed the presence of extensive DVT extending to the lower segment of the inferior vena cava. Spine magnetic resonance imaging showed abnormal enhancement of the conus medullaris with thick enhanced cauda equina nerve roots, consistent with a possible case of Guillain-Barré syndrome. However, there was engorgement of the EVP extending to the ascending lumbar, azygos, and hemiazygos veins, which was misdiagnosed. The patient was managed immediately with low-molecular-weight heparin and steroids. She died 4 weeks after admission due to hospital-acquired pneumonia and acute respiratory distress syndrome, probably due to the high dose of steroids. Conclusions: Acute CES has a wide differential diagnosis. This report describes an unusual cause of CES and emphasizes the importance of early recognition to avoid misdiagnosis and management delay. Early identification of this clinical entity markedly decreases morbidity and mortality and thus improves the prognosis. Likewise, underlying causing factors such as venous congestion due to OCCP-related DVT should be considered in the diagnosis.

Case Reports in Neurological Medicine, 2017

Polyostotic sclerosing histiocytosis, also known as Erdheim-Chester disease (ECD), is a rare form... more Polyostotic sclerosing histiocytosis, also known as Erdheim-Chester disease (ECD), is a rare form of non-Langerhans histiocytosis. ECD has wide clinical spectrums which mainly affect skeletal, neurological, dermatological, retroperitoneal, cardiac, and pulmonary manifestations. Here we describe a case of ECD in a 45-year-old female who presented initially with bilateral knee pain and homonymous superior quadrantanopia progressed to ophthalmoplegia and complete visual loss of the left eye over a period of one year. Plain X-ray of both knees showed bilateral patchy sclerosis of the distal femur and upper parts of the tibiae. Initial brain magnetic resonance imaging (MRI) showed bilateral enhancing masses in the temporal lobes anterior to the temporal horns, thickening of the pituitary stalk, partially empty sella, and involvement of the left cavernous sinus one year later. Our case is a peculiar case of ECD initially presented with unilateral homonymous superior quadrantanopia due to ...

Annals of Saudi Medicine, 1996

Saudi Medical Journal, Oct 1, 2006

In this report, we describe a patient with left conjugate gaze palsy and internuclear ophthalmopl... more In this report, we describe a patient with left conjugate gaze palsy and internuclear ophthalmoplegia on the opposite gaze one-and-a-half-syndrome [11/2 syndrome]. Magnetic resonance imaging of the brain showed nodular enhancing brain stem lesions. After excluding other potential diseases, tuberculoma was thought to be the underlying etiology. Recovery was achieved 8 weeks after initiation of anti-tuberculous anti-TB therapy. The isolated nature of the tuberculoma and the association with this rare syndrome is highlighted.

Neurosciences (Riyadh, Saudi Arabia), 2000

The association between acute rise of blood pressure and encephalopathy with early recognition, a... more The association between acute rise of blood pressure and encephalopathy with early recognition, and therapy reversibility has been reported. We reported a case of a young lady in postnatal period, presented with acute rise of blood pressure, encephalopathy, quadriparesis, and apraxia. Magnetic resonance imaging of the brain showed hyperintense lesions in occipital, parietal and right temporal areas. Cerebral angio showed multiple segmental vasoconstriction and narrowing of intracerebral vessels. Immediate control of blood pressure enhanced recovery but it is incomplete.

Neurosciences (Riyadh, Saudi Arabia), 2002

Neuromyelitis optica disease is characterized by simultaneous or successive attacks involving bot... more Neuromyelitis optica disease is characterized by simultaneous or successive attacks involving both the optics nerves and spinal cord without any evidence of the disease elsewhere. We report a 22-year-old Saudi woman with relapsing neuromyelitis optica disease. She had all the clinical, cerebrospinal fluid, and radiological features that differ from primary demyelinating disease. However, our patient responded well to long-term corticosteroid therapy and azathioprine with improvement in her expanded disability status scale, and ambulation. In addition, no acute relapses occurred with significant improvement on magnetic resonance imaging lesions and favorable outcome.

Neurosurgery Rounds: Questions and Answers, 2011

Neurology, 2006

Pelizaeus-Merzbacher-like disease (PMLD) is an inherited hypomyelinating leukoencephalopathy with... more Pelizaeus-Merzbacher-like disease (PMLD) is an inherited hypomyelinating leukoencephalopathy with onset in early infancy. Like Pelizaeus-Merzbacher disease (PMD), PMLD is characterized clinically by nystagmus, cerebellar ataxia, and spasticity, due to a permanent lack of myelin deposition in the brain. Mutations in the GJA12 gene, encoding connexin 47 (Cx47), were recently reported in five children with autosomal recessive PMLD. To evaluate the impact of mutations in the GJA12 gene in, and define the clinical and neuroimaging features of, autosomal recessive PMLD. The authors screened for GJA12 mutations in 10 additional PMLD families originating from Italy, Pakistan, and Saudi Arabia. Three novel homozygous GJA12 mutations were identified in 12 mutant cases distributed in 3 of 10 families. The mutations segregated with the disease according to an autosomal recessive trait and included one missense (G236S) and two nonsense (L281fs285X and P131fs144X) changes. The identification of homozygous mutations predicting the synthesis of aberrant and truncated polypeptides, and their tight segregation with the disease in very large families, clearly demonstrate that the loss of Cx47 function is the cause of the disease. The phenotype of GJA12-related Pelizaeus-Merzbacher-like disease is fairly homogeneous and similar to that of Pelizaeus-Merzbacher disease. However, slower progression of symptoms, greater preservation of cognitive functions, and partial myelination of corticospinal tracts at MRI were distinctive features, which could help in the differential diagnosis.

The Journal of Pediatrics, 2014

Objective To determine the frequency of mitochondrial DNA depletion syndrome (MDS) in infants wit... more Objective To determine the frequency of mitochondrial DNA depletion syndrome (MDS) in infants with cholestasis and liver failure and to further clarify the clinical, biochemical, radiologic, histopathologic, and molecular features associated with MDS due to deoxyguanosine kinase (DGUOK) and MPV17 gene mutations. Study design We studied 20 infants with suspected hepatocerebral MDS referred to our tertiary care center between 2007 and 2013. Genomic DNA was isolated from blood leukocytes, liver, and/or skeletal muscle samples by standard methods. Mitochondrial DNA copy number relative to nuclear DNA levels was determined in muscle and/ or liver DNA using real-time quantitative polymerase chain reaction and compared with age-matched controls. Nuclear candidate genes, including polymerase g, MPV17, and DGUOK were sequenced using standard analyses. Results We identified pathogenic MPV17 and DGUOK mutations in 11 infants (6 females) representing 2.5% of the 450 cases of infantile cholestasis and 22% of the 50 cases of infantile liver failure referred to our center during the study period. All of the 11 patients manifested cholestasis that was followed by a rapidly progressive liver failure and death before 2 years of life. Mitochondrial DNA depletion was demonstrated in liver or muscle for 8 out of the 11 cases where tissue was available. Seven patients had mutations in the MPV17 gene (3 novel mutations), 4 patients had DGUOK mutations (of which 2 were novel mutations). Conclusion Mutations in the MPV17 and DGUOK genes are present in a significant percentage of infants with liver failure and are associated with poor prognosis.

Head & Neck Oncology, 2011

Fibrous dysplasia (FD) and aneurysmal bone cyst (ABC) are uncommon benign intraosseous lesions. S... more Fibrous dysplasia (FD) and aneurysmal bone cyst (ABC) are uncommon benign intraosseous lesions. Simultaneous occurrence of both lesions is extremely rare. We present an example of concomitant FD and ABC in a 7 year-old with left eye blindness and discharge of one month duration. Physical examination revealed a proptotic left eye and bulging of the hard palate. CT and MRI are consistent with FD and ABC that involved the sphenoid and ethmoidal bones bilaterally. Incomplete combined endonasalcranial resection was performed. The patient presented five months postoperatively with a large recurrence and subsequent follow up was lost. Concomitant FD with ABC may occur in paranasal sinuses and may develop rapidly and exhibit locally aggressive behavior.

Annals of Saudi Medicine, 1996

Case reports in pediatrics, 2017

Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy ... more Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing's sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT) imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) seeding from the L5 to the S4 vertebrae. Primary cranial Ewing's sarcoma is considered ...

American Journal of Human Genetics, 2008

Cytochrome c oxidase (COX) deficiency, one of the most common respiratory-chain defects in humans... more Cytochrome c oxidase (COX) deficiency, one of the most common respiratory-chain defects in humans, has been associated with mutations in either mitochondrial DNA genes or nucleus-encoded proteins that are not part in but promote the biogenesis of COX. Mutations of nucleus-encoded structural subunits were sought for but never found in COX-defective patients, leading to the conjecture that they may be incompatible with extra-uterine survival. We report a disease-associated mutation in one such subunit, COX6B1. Nuclear-encoded COX genes should be reconsidered and included in the diagnostic mutational screening of human disorders related to COX deficiency.