OBJECTIVE: To explore the genotype-phenotype correlation of a Chinese pedigree affected with Lowe syndrome. METHODS: Whole exome sequencing (WES) and Sanger sequencing were carried out for the proband and members of his pedigree. RESULTS: The proband, a 3-year-and-5-month-old male, presented with multiple anomalies including congenital cataract, glaucoma, brain dysplasia, renal dysfunction and cognitive impairment. WES revealed that he has harbored a novel hemizygous missense variant of the OCRL gene, namely NM_000276.3: c.1255T>C (p.Trp419Arg) (GRCh37/hg19), which was derived from his unaffected mother. The same variant was not found in his elder brother who was healthy. The variant was predicted to be pathogenic according to ACMG/AMP guideline. Compared with previously reported cases of Lowe syndrome, our patient has displayed rare features including corpus callosum dysplasia, reduction of white matter, cerebral hypoplasia, laryngomalacia, sebaceous cyst, recurrent eczema, cryptorchidism, hypoglycemia and irritability. CONCLUSION Above finding has expanded the mutational spectrum of the OCRL gene, enriched clinical features of Lowe syndrome, and enabled genetic counseling for this pedigree.
Aged ; China ; Genetic Association Studies ; Humans ; Infant ; Male ; Mutation ; Oculocerebrorenal Syndrome ; Pedigree ; Phosphoric Monoester Hydrolases/genetics* ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic etiology for a child with ocular dysplasia. METHODS: Clinical examination was carried out. Medical history of the child was collected. Genomic DNA was extracted from peripheral blood samples. Chromosomal microarray analysis (CMA) was used to detect potential genomic copy number variations. RESULTS: Ultrasonography revealed cataracts in both eyes of the child. MRI showed increased extracranial space, supratentorial ventricular dilatation, reduced white matter volume, increased T2WI signal and a large occipital cisterna. CMA showed that the patient carried a 249 kb microdeletion at Xq25q26.1 region, namely [hg19]arrXq25q26.1 (128 652 372 - 128 901 629)×0. CONCLUSION The child was diagnosed with Lowe syndrome, for which the 249 kb microdeletion at Xq25q26.1 is probably accountable.
Child ; Chromosome Aberrations ; DNA Copy Number Variations ; Humans ; Microarray Analysis ; Oculocerebrorenal Syndrome

OBJECTIVETo report on a sporadic case of Lowe syndrome diagnosed prenatally with ultrasound examination and genetic testing.

METHODSDetailed sonographic fetal screening was performed by an experienced sonographer at 32 weeks of gestation. Fetal cranial magnetic resonance imaging (MRI) was applied to detect potential brain abnormality. Chromosomal microarray analysis (CMA) was conducted on amniotic fluid sample from the fetus and peripheral blood sample from the mother.

RESULTSCongenital cataract and enlarged posterior fossa were detected by fetal ultrasound screening. Fetal cranial MRI found hypoplasia of the gyrus. CMA revealed that the fetus has carried a 633 kb deletion at Xq25-26.1 which encompassed the OCRL gene. The mother was a carrier of the same deletion. Clinical examination after birth confirmed that the neonate was affected with Lowe syndrome in addition with an atrial septal defect.

CONCLUSIONPrenatal diagnosis of Lowe syndrome without a family history largely depends on fetal imaging. Should cataract be found by ultrasound screening, fetal MRI may be considered to rule out central nervous system anomalies. CMA assay should also be considered to facilitate the diagnosis.

Adult ; Child ; Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, X ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Infant ; Male ; Microarray Analysis ; Oculocerebrorenal Syndrome ; diagnosis ; embryology ; genetics ; Phosphoric Monoester Hydrolases ; genetics ; Pregnancy ; Prenatal Diagnosis ; Ultrasonography, Prenatal

Humans ; Oculocerebrorenal Syndrome ; diagnosis

PURPOSE: Lowe syndrome is a rare, X-linked recessive disorder caused by mutations in the OCRL gene. It involves multiple anatomic systems, particularly the eyes, central nervous system, and kidneys, and leads to profound growth failure and global developmental delay. This study evaluated the clinical and genetic characteristics of Korean patients with Lowe syndrome. METHODS: The clinical findings and results of genetic studies were reviewed for 12 male patients diagnosed with Lowe syndrome at a single medical institution. RESULTS: The mean age of the patients at presentation was 2.2 months (range, 0-4 months), although the diagnosis was delayed by a mean of 2.8 years (range, 0-9.7 years). The mean follow-up period was 9.0 years (range, 0.6-16.7 years). Nine mutations in OCRL were identified in 11 patients (92%), with three novel mutations. The main presentation was congenital cataract in both eyes necessitating early cataract removal in the 11 patients with impaired visual acuity. Profound short stature and developmental delay were observed in all patients, and seizures occurred in 50% of the patients. All patients suffered from proximal renal tubular dysfunction, and one patient developed chronic renal failure. Other manifestations included pathologic fracture (50%), cutaneous cysts (42%), and cryptorchidism (42%). However, there was no bleeding tendency, and none of the patients died during the study period. CONCLUSION: This study describes the clinical and genetic characteristics of Korean patients with Lowe syndrome. The observations are helpful for understanding the natural courses of Lowe syndrome and for appropriate genetic counseling.
Acidosis ; Cataract ; Central Nervous System ; Cryptorchidism ; Developmental Disabilities ; Diagnosis ; Fanconi Syndrome ; Follow-Up Studies ; Fractures, Spontaneous ; Genetic Counseling ; Hemorrhage ; Humans ; Kidney ; Kidney Failure, Chronic ; Korea ; Male ; Oculocerebrorenal Syndrome* ; Seizures ; Visual Acuity

Oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked recessive disorder. This study investigated the history of a Chinese family with OCRL and used direct DNA sequencing to screen all exons of OCRL gene for mutations. A missense mutation (1736 A→G) in exon 15 was revealed, which resulted in the change of His (H) 507 to Arg (R). The patient's mother was the carrier of the heterozygous mutation in X-chromosome. To our knowledge, H507R mutation in OCRL gene has not been reported in Chinese people.
DNA Mutational Analysis ; Humans ; Infant ; Male ; Mutation, Missense ; Oculocerebrorenal Syndrome ; genetics ; Phosphoric Monoester Hydrolases ; genetics

OBJECTIVETo identify pathological mutation in a Chinese male infant featuring oculocerebrorenal syndrome (also called Lowe syndrome).

METHODSClinical data of the patient were collected. DNA was extracted from peripheral blood of the infant and his parents. All of the 24 exons and intron-exon splice sites of OCRL gene were amplified with PCR. Mutations were detected by direct sequencing the PCR products.

RESULTSThe infant was found to have carried a c.1499G>A (p.R500Q) mutation in exon 15 of the OCRL gene, which was transmitted from his mother, who was heterozygous for the same mutation. The c.1499G>A mutation, discovered in Chinese population for the first time, has been reported to cause severe Lowe syndrome in other ethnic populations.

CONCLUSIONThe c.1499G>A mutation of the OCRL gene is probably responsible for the disease in the patient. Further study of this mutation may facilitate delineation of the genotype-phenotype correlation of this disease.

Humans ; Infant ; Male ; Mutation ; Oculocerebrorenal Syndrome ; genetics ; Phosphoric Monoester Hydrolases ; genetics

Child ; Codon, Nonsense ; genetics ; DNA Mutational Analysis ; DNA Primers ; genetics ; Dent Disease ; diagnosis ; genetics ; Exons ; genetics ; Humans ; Infant ; Male ; Mutation ; Oculocerebrorenal Syndrome ; diagnosis ; genetics ; Phosphoric Monoester Hydrolases ; genetics ; Polymerase Chain Reaction

Lowe syndrome is a rare genetic condition that involves three major organs: eyes, brain, and kidney. Anesthetic management can be challenged by problems associated with high ocular pressure, mental retardation, and renal tubular dysfunction. We report a case of a 17 year-old boy with Lowe syndrome accompanied by end-stage renal disease who underwent general anesthesia for arteriovenous fistula formation. The Anesthetic implications of this syndrome are also described.
Anesthesia ; Anesthesia, General ; Arteriovenous Fistula ; Brain ; Eye ; Humans ; Intellectual Disability ; Kidney ; Kidney Failure, Chronic ; Oculocerebrorenal Syndrome ; Quaternary Ammonium Compounds

Lowe syndrome is a rare genetic disease that appears to cause various clinical symptoms involving the eye, nervous system, and kidney. While a mutation of the OCRL1 gene is known to be responsible for this syndrome, the exact pathophysiology remains unclear. Various multi-organ symptoms are characteristic of Lowe syndrome, but skin lesions have rarely been described. Recently, mechanisms for the association of Lowe syndrome and skin lesions have been proposed. We report this case of Lowe syndrome involving multiple epidermal cysts on the scalp in a 6-year-old male child.
Child ; Epidermal Cyst ; Eye ; Humans ; Kidney ; Male ; Nervous System ; Oculocerebrorenal Syndrome ; Scalp ; Skin