21308977 Visualization

The patient was a 3 Age - year Age - old Age girl Sex with the following features of VACTERL Diagnostic_procedure association Diagnostic_procedure : absent Detailed_description C1 Biological_structure vertebra Biological_structure , supernumerary Detailed_description lumbar Biological_structure vertebrae Biological_structure , hypoplastic Detailed_description sacrum Biological_structure / coccyx Biological_structure , fatty Detailed_description filum Biological_structure terminale Biological_structure with tethered Detailed_description spinal Biological_structure cord Biological_structure , and three Lab_value fused Detailed_description ribs Biological_structure ; an anorectal Disease_disorder malformation Disease_disorder including a cloaca Biological_structure consisting of a common Detailed_description urogenital Biological_structure sinus Biological_structure and a duplex Detailed_description vagina Biological_structure with midline Detailed_description septum Detailed_description ; type Detailed_description C Detailed_description TE Disease_disorder fistula Disease_disorder ; right Biological_structure renal Biological_structure agenesis Disease_disorder with moderate Severity left Detailed_description hydronephrosis Disease_disorder and vesicoureteral Disease_disorder reflux Disease_disorder .
She had no cardiac Disease_disorder or limb Disease_disorder malformations Disease_disorder , and no other Disease_disorder major Disease_disorder organ Disease_disorder anomalies Disease_disorder .
Both she Other_entity and her Subject father Subject were additionally clinically diagnosed with hypermobile Detailed_description type Detailed_description Ehlers Disease_disorder – Danlos Disease_disorder syndrome Disease_disorder , but family history was otherwise noncontributory.
The diagnosis of hypermobile Detailed_description type Detailed_description Ehlers Disease_disorder – Danlos Disease_disorder was based on the patient’s hypermobility Disease_disorder ( 9/9 Lab_value on the Beighton Diagnostic_procedure hypermobility Diagnostic_procedure scale Diagnostic_procedure ), very Lab_value soft Texture , fragile Texture skin Biological_structure with unusual Detailed_description scarring Detailed_description , and poor Lab_value skin Detailed_description healing Detailed_description .
Skin Biological_structure biopsy Diagnostic_procedure was not performed, but testing Diagnostic_procedure on peripheral Biological_structure blood Biological_structure did not reveal mutations Diagnostic_procedure associated with other Detailed_description forms Detailed_description of Ehlers Disease_disorder – Danlos Disease_disorder syndrome Disease_disorder .
Microarray Diagnostic_procedure analysis Diagnostic_procedure initially showed a maternally Detailed_description - inherited Detailed_description deletion Diagnostic_procedure at 4q35.1 Biological_structure detected with one Diagnostic_procedure clone Diagnostic_procedure and confirmed by FISH Diagnostic_procedure (RP11 Diagnostic_procedure - 173M11) Diagnostic_procedure .
Subsequent performance of an 180K Diagnostic_procedure custom Diagnostic_procedure oligonucleotide Diagnostic_procedure microarray Diagnostic_procedure ( Baylor Nonbiological_location College Nonbiological_location of Nonbiological_location Medicine Nonbiological_location Medical Nonbiological_location Genetics Nonbiological_location Laboratories Nonbiological_location ) refined the deleted Diagnostic_procedure region Diagnostic_procedure deletion Diagnostic_procedure to a maximum Lab_value size Lab_value of Lab_value 1.37 Lab_value Mb Lab_value , with karyotype Diagnostic_procedure revised to 46,XX,arr Detailed_description cgh Detailed_description 4q35.1q35.2 Detailed_description (187,321 Detailed_description - 768 Detailed_description - 188,694 Detailed_description - 589) Detailed_description 3 Detailed_description 1 Detailed_description .
Genes Diagnostic_procedure in the deleted Detailed_description region Detailed_description , which contains a number of much smaller copy number variations (CNVs) identified in normal controls, include CYP4V2 Diagnostic_procedure , KLKB2 Diagnostic_procedure , F11 Diagnostic_procedure , MTRNR1A Diagnostic_procedure , and FAT1 Diagnostic_procedure , none of which can be clearly related to her phenotype, especially as her Subject mother Subject , from Detailed_description whom Detailed_description the Detailed_description deletion Detailed_description was Detailed_description inherited Detailed_description , is unaffected Disease_disorder .
Evidence for mitochondrial Disease_disorder dysfunction Disease_disorder began at 13 Age months Age of Age age Age with progressive Detailed_description muscle Sign_symptom weakness Sign_symptom , autonomic Disease_disorder dysregulation Disease_disorder , hypoglycemic Disease_disorder episodes Disease_disorder , exocrine Disease_disorder pancreatic Disease_disorder dysfunction Disease_disorder , and decline Detailed_description of gastrointestinal Diagnostic_procedure function Diagnostic_procedure , eventually leading to total Severity parenteral Detailed_description nutrition Disease_disorder dependency Disease_disorder due to visceral Biological_structure hyperalgesia Disease_disorder , dysmotility Disease_disorder , and malabsorption Disease_disorder .
Muscle Biological_structure biopsy Diagnostic_procedure showed a mild Severity increase Lab_value in fiber Diagnostic_procedure size Diagnostic_procedure variability Diagnostic_procedure but no other Diagnostic_procedure findings Diagnostic_procedure consistent Detailed_description with Detailed_description mitochondrial Detailed_description disease Detailed_description , including via electron Diagnostic_procedure microscopy Diagnostic_procedure .
However, analysis of electron Diagnostic_procedure transport Diagnostic_procedure chain Diagnostic_procedure (ETC) Diagnostic_procedure activity Diagnostic_procedure showed normal Lab_value activity of complexes Diagnostic_procedure I Diagnostic_procedure , II Diagnostic_procedure , and III Diagnostic_procedure , but complex Diagnostic_procedure IV Diagnostic_procedure , or cytochrome Diagnostic_procedure c Diagnostic_procedure oxidase Diagnostic_procedure , activity was 45.4 Lab_value lmol/min/g Lab_value weight Lab_value , well Detailed_description below Detailed_description the Detailed_description control Detailed_description range Detailed_description (148.9 +/− 67.2 lmol/min/g weight).
Repeat Detailed_description ETC Diagnostic_procedure analysis Diagnostic_procedure in isolated Detailed_description mitochondria Biological_structure confirmed a profound Severity and reproducible Detailed_description complex Disease_disorder IV Disease_disorder deficiency Disease_disorder .
Citrate Diagnostic_procedure synthase Diagnostic_procedure activity Diagnostic_procedure and content Diagnostic_procedure in both Coreference ETC Coreference analyses Coreference were normal Lab_value , confirming good Lab_value sample Diagnostic_procedure quality Diagnostic_procedure and normal Lab_value mitochondrial Diagnostic_procedure content Diagnostic_procedure .
Whole Detailed_description mitochondrial Biological_structure genome Diagnostic_procedure sequencing Diagnostic_procedure , and sequencing Diagnostic_procedure of DNA Diagnostic_procedure Polymerase Diagnostic_procedure Gamma Diagnostic_procedure 1 Diagnostic_procedure and 2 Diagnostic_procedure ( POLG1 Diagnostic_procedure and POLG2 Diagnostic_procedure ) and Thymidine Diagnostic_procedure Phosphorylase Diagnostic_procedure did not reveal abnormalities.