NA24529
DNA from Fibroblast
Description:
ATAXIA AND CEREBELLAR HYPOPLASIA
MITOCHONDRIAL COMPLEX I DEFICIENCY
NUCLEOTIDE-BINDING PROTEIN-LIKE PROTEIN; NUBPL
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
PIGI Consented Sample |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Skin
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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DNA from Fibroblast
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Race
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White
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Ethnicity
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Not Hispanic/Latino
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Ethnicity
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GERMAN
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Country of Origin
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USA
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Family Member
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1
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Family History
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Y
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
5.17 |
| Passage Frozen |
2 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| Gene |
NUBPL |
| Chromosomal Location |
14q12 |
| Allelic Variant 1 |
Substitution; MITOCHONDRIAL COMPLEX I DEFICIENCY |
| Identified Mutation |
c.311T>C; Respiratory complex I (NADH:ubiquinone oxidoreductase; EC 1.6.5.3) is a large mitochondrial inner membrane enzyme consisting of 45 subunits and 8 iron-sulfur (Fe/S) clusters. NUBPL, or IND1, is an Fe/S protein that plays a critical role in the assembly of respiratory complex I, likely by transferring Fe/S into the Fe/S-containing complex I subunits |
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| Gene |
NUBPL |
| Chromosomal Location |
14q12 |
| Allelic Variant 1 |
splice defect; MITOCHONDRIAL COMPLEX I DEFICIENCY |
| Identified Mutation |
c.815-27T>C; Respiratory complex I (NADH:ubiquinone oxidoreductase; EC 1.6.5.3) is a large mitochondrial inner membrane enzyme consisting of 45 subunits and 8 iron-sulfur (Fe/S) clusters. NUBPL, or IND1, is an Fe/S protein that plays a critical role in the assembly of respiratory complex I, likely by transferring Fe/S into the Fe/S-containing complex I subunits |
| Remarks |
Clinically affected; diagnosed by geneticist at 14 years of age; onset of symptoms at birth; born via vaginal delivery at 41 weeks gestation; perinatal complications resulting from nuchal cord, requiring oxygen; exposure to amphetamine until approximately 6 weeks gestation; Apgar scores were 5 and 9; ataxia; ataxia of the hands; clonus; pons hypoplasia; moderate to severe cerebellar hypoplasia; nystagmus; hyperrelexia; pes planus, talipes valgus(club feet); seizures; onset of tremulousness and rigidity at 3 months of age; developmental milestone delay; gross motor delays; Developmental history: smiled at 6 weeks; reached at 7 months; at age 9 months subject had poor head control, unable to sit with support, unable to crawl and unable to pull to a stand; rolling back without support at 12 months; stood independently at 30 months; walked at 4 years; toilet trained at 8 years; speech delay: first words at 30 months; at age 13: reasonably good vocabulary and in special day class at school; Diagnostic tests: MRI revealed diffuse bilateral abnormal signal from the cortices of the cerebellar hemisphere; cerebral biopsy revealed swollen Purkinje cells; subsequent MRIs show severe global prominence of the sulci in the right and left cerebella line with T2 prolongation, as well as diffuse hypoplasia/atrophy of the cerebellum, absent vermis and enlarged unusually shaped 4th ventricle; automated fluorescent dideoxy exome sequencing revealed compound heterozygous alterations of the NUBPL gene: c.311T>C (p.L104P) in exon 4 and c.815-27T>C in intron 9 in the splicing site; the c.311T>C missense alteration is located at a highly conserved amino acid and is predicted to be deleterious by SIFT and PolyPhen; the c.815-27T>C alteration is located at a highly conserved nucleotide; in vitro analyses via mRNA, protein expression, and RT-PCR demonstrate splicing defects (resulting in a frameshift) and reduced mRNA and protein levels; therapies include: physical/occupational therapy, and speech language therapy; surgical procedures include: foot reconstruction (arch construction); treatments include: levocarnitine, Coenzyme Q10, mitochondrial cocktail therapy, biotin, alpha lipoic acid, and vitamins E, C and B complex; family history: one unaffected sister, one sister affected with similar symptoms although less severely (also found to carry both mutations), the father carries the c.815-27T>C alteration, the mother carries the c.311T>C (p.L104P) alteration.
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| Patgiri A, Skinner OS, Miyazaki Y, Schleifer G, Marutani E, Shah H, Sharma R, Goodman RP, To TL, Robert Bao X, Ichinose F, Zapol WM, Mootha VK, An engineered enzyme that targets circulating lactate to alleviate intracellular NADH:NAD Nature biotechnology: 2019 |
| PubMed ID: 31932725 |
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| Johnson SC, Martinez F, Bitto A, Gonzalez B, Tazaerslan C, Cohen C, Delaval L, Timsit J, Knebelmann B, Terzi F, Mahal T, Zhu Y, Morgan PG, Sedensky MM, Kaeberlein M, Legendre C, Suh Y, Canaud G, mTOR inhibitors may benefit kidney transplant recipients with mitochondrial diseases Kidney international: 2018 |
| PubMed ID: 30471880 |
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