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At least 1,549 records · Page 86Linked to original sources
PubMed1993

Unilateral lateral rectus recessions in exotropia.

For the past several years, we have been performing unilateral lateral rectus recessions in patients with small- to moderate-angle intermittent or constant exotropia. We report a 73% success rate in 45 patients undergoing 6- to 10-millimeter unilateral lateral rectus recessions in exotropia with a minimum of 6 months' follow up. The success rate increased to 89% for patients under 4 years of age. The advantages of this procedure include operating on only one eye and virtual elimination of overcorrections, thereby preventing early postoperative consecutive esotropia, which occasionally can result in amblyopia or diminished stereopsis in very young children.

Adolescent↗
PubMed1997

mtDNA analysis shows common ancestry in two kindreds with X-linked recessive hypoparathyroidism and reveals a heteroplasmic silent mutation.

Two kindreds residing in eastern Missouri and exhibiting X-linked recessive idiopathic hypoparathyroidism have been described. Genealogical records extending back five generations revealed no common ancestor. To investigate the possibility of relatedness, the DNA sequence of the mitochondrial D-loop was compared among several individuals in both kindreds. The mtDNA D-loop was amplified from the total DNA of individuals by use of nested PCR reactions, and the resulting 430-bp fragment was sequenced. The mtDNA sequence was identical among affected males and their maternal lineage for individuals in both kindreds. Conversely, the mtDNA sequence of the fathers of the affected males differed from that of the maternal lineage at three to six positions. These results demonstrate that the two kindreds exhibiting X-linked recessive hypoparathyroidism are indeed related and that an identical gene defect is responsible for the disease. A further feature of the inheritance pattern was examined when a unique point mutation was identified in the mtDNA of one branch of one of the kindreds. This mutation appears to be de novo and segregates in subsequent generations without obscuring relatedness. In addition, the results of our study of mtDNA analysis indicate that this approach may be of importance in investigating common ancestry in other X-linked disorders.

Alleles↗
PubMed1997

Family with branchial arch anomalies, hearing loss, ear and commissural lip pits, and rib anomalies. A new autosomal recessive condition: branchio-oto-costal syndrome?

We report on a family in which 3 sibs were affected with conductive deafness, bilateral preauricular and commissural lip pits, monolateral branchial fistula, and rib anomalies. On the basis of parental consanguinity, lack of clinical variability and affected subjects of both sexes, this condition seems to be inherited as an autosomal recessive trait. We suggest that these findings comprise a new autosomal recessive entity of branchial, auricular and costal anomalies, for which we suggest the acronym BOC (branchio-oto-costal) syndrome.

Abnormalities, Multiple↗
PubMed1997

Investigations on subjective and objective cyclorotatory changes after inferior oblique muscle recession.

PURPOSE: To determine subjective and objective cyclorotatory changes after surgery for oblique muscle disorders and to analyze the mechanisms of the well-known, long-term, postoperative, subjective cyclotorsional changes. METHODS: Twenty-six patients underwent unilateral inferior oblique muscle recession for strabismus sursoadductorius (inferior oblique overfunction). Subjective and objective cyclodeviation were examined before surgery with and without diagnostic occlusion, as well as 1 day, 3 days, and 4 months after surgery. Subjective cyclodeviation was assessed by Harms' tangent scale. Objective cycloposition was measured by means of fundus cyclometry, a novel method using an infrared scanning laser ophthalmoscope. RESULTS: Diagnostic occlusion did not lead to significant changes in either objective or subjective cyclodeviation. Preoperative objective excycloposition was nearly equally distributed between affected eyes and fellow eyes. Early surgically induced incyclorotatory effects were more pronounced objectively than subjectively. On long-term follow-up, a reduction in the incyclorotatory effect was found to be smaller subjectively than objectively. A significant difference between subjective and objective cycloposition was seen early after surgery, and a significant difference between subjective and objective cyclorotatory change was found immediately after surgery and on long-term follow-up. CONCLUSIONS: Long-term regression of the incyclorotatory effect after inferior oblique muscle recession was confirmed objectively and subjectively and can be explained as a cessation of preoperatively required binocular compensatory innervation. The authors conclude that the difference between objective and subjective regression is caused by sensory cyclofusion.

Adolescent↗
PubMed1997

Outcome study of bilateral lateral rectus recession for intermittent exotropia in children.

PURPOSE: This paper reports an outcome study of 52 consecutive children treated by bilateral lateral rectus recession for intermittent exotropia over a 9 year period (1981-90) with a minimum follow up of 6 months. METHODS: Successful alignment was defined as the absence of any postoperative intermittent or constant tropia in any position of gaze. The study examined the variables that might be predictive of successful alignment. The charts were abstracted for age at initial surgery, quantity of initial deviation, initial refraction, motor alignment at 1 week and 6 months, final alignment, secondary surgery results and the incidence of a monofixation syndrome result. RESULTS: Motor tests demonstrated that 32 (62%) of the patients were successfully aligned by the initial procedure performed for a mean of 25 prism diopters of preoperative deviation while viewing distant targets at a mean age of 4 years 8 months, followed for a mean of 4 years, 4 months. The incidence of undercorrections and overcorrections were approximately equal in quantity suggesting that the current surgical dosage was adequate, but the age at initial surgery, initial deviation, initial refraction and 1 week postoperative alignment results were not predictive of success. Alignment at 6 months, however, was highly correlated with successful alignment by the end of the study (p = 0.002). Secondary surgery was performed for 11 patients and 5 patients were found to have a monofixation syndrome result. CONCLUSION: Successful alignment was achieved in the majority of children treated for intermittent exotropia by an initial bilateral lateral rectus recession. However, 20% of the patients received secondary surgery for a residual deviation, and the study confirmed a previously reported 10% incidence of monofixation syndrome result in children surgically treated for this type of strabismus.

Child↗
PubMed1998

In vivo tissue pO2 measurements in hamster skinfold by recessed pO2 microelectrodes and phosphorescence quenching are in agreement.

OBJECTIVE: Phosphorescence quenching has been used successfully to optically measure in vivo blood pO2 in the microvasculature. Optical measurements have also been made in some tissues, but it is not clear whether these results accurately reflect tissue pO2. METHODS: Recessed pO2 microelectrodes and the phosphorescence quenching technique were used simultaneously to measure in vivo tissue pO2 in hamster skinfold. The optical window for phosphorescence quenching was focused around the tips of microelectrodes that were positioned in tissue regions at least 100 microns from large microvessels. RESULTS: Mean tissue pO2 measured by recessed pO2 microelectrodes was 18.4 +/- 1.7 (SE) Torr, and mean tissue pO2 determined from the time course of phosphorescence decay was 18.8 +/- 2.0 Torr (no significant difference). The two tissue pO2 measurements agreed over a wide range, from 2 to 46 Torr (r = 0.93, 39 paired measurements from six sites in 3 animals). There was no systematic change in the microelectrode tissue pO2 during the period of light excitation used for the optical method. CONCLUSIONS: Under the conditions of our study, sufficient amounts of porphyrin dye leaked from the vasculature and diffused into tissue, allowing accurate measurements of tissue pO2 by the phosphorescence quenching technique. Furthermore, the optical method did not deplete significant amounts of O2 from tissue during light excitation.

Animals↗
PubMed2005

Algorithm for efficient PKHD1 mutation screening in autosomal recessive polycystic kidney disease (ARPKD).

Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of childhood renal- and liver-related morbidity and mortality with variable disease expression. While most cases manifest peri-/neonatally with a high mortality rate in the first month of life, others survive to adulthood. ARPKD is caused by mutations in the Polycystic Kidney and Hepatic Disease 1 (PKHD1) gene on chromosome 6p12. PKHD1 is an exceptionally large gene (470 kb) with a longest open reading frame transcript of 67 exons predicted to encode a 4,074-amino acid (aa) (447 kDa) multidomain integral membrane protein (fibrocystin/polyductin) of unknown function. Recent DHPLC-based mutational studies have reported detection rates of about 80% and a minimum of one PKHD1 mutation in more than 95% of families. Thus far, a total of 263 different PKHD1 mutations (639 mutated alleles) are included in the locus-specific database (www.humgen.rwth-aachen.de). Except for a few population-specific founder alleles and the common c.107C>T (p.Thr36Met) missense change, PKHD1 is characterized by significant allelic diversity, making mutation screening time-consuming and labor-intensive. Mutations are distributed throughout the gene's coding sequence; however, they are not equally scattered. Thus, we aimed to set up an algorithm for efficient molecular genetic diagnostics in ARPKD. A total of 80% of known PKHD1 mutations can be identified if a subset of 27 out of 77 DHPLC fragments is screened. The current study provides an essential platform for PKHD1 mutation screening in a routine setting that will largely alleviate molecular genetic diagnostics in patients suspected to have ARPKD.

Algorithms↗
PubMed2025

Severe hypercholesterolemia in a pediatric cohort: Familial homozygous and autosomal recessive hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder characterized by impaired clearance of low-density lipoprotein cholesterol (LDL-C), leading to severe hypercholesterolemia and increased risk of premature cardiovascular disease (CVD). Our study aims to describe and compare the clinical, biochemical, and genetic profiles of pediatric patients diagnosed with FH based on LDL-C levels exceeding 400 mg/dL (10.4 mmol/L) and confirmed by biallelic pathogenic variants in low-density lipoprotein receptor (LDLR) or low-density lipoprotein receptor adapter protein-1 (LDLRAP1) genes. METHODS: This retrospective cohort study included 39 pediatric patients diagnosed with FH at a tertiary care center. Clinical data were analyzed, including age at diagnosis, family history, lipid profile, presence of xanthomas, and cardiovascular complications. Molecular analysis was conducted using next-generation sequencing (NGS) and Sanger sequencing to confirm pathogenic variants. Statistical comparisons were performed between the LDLR and LDLRAP1 variant groups regarding lipid profiles, treatment response, and cardiovascular outcomes. RESULTS: Among 39 patients, 32 and 7 had pathogenic variants in LDLR and LDLRAP1 genes, respectively. Genetic analysis identified 27 unique pathogenic variants in LDLR (including 5 novel mutations) and 4 in LDLRAP1 causal for autosomal recessive hypercholesterolemia (ARH), highlighting the molecular diversity of FH. Compared to the LDLR variant group, LDLRAP1 variant patients had significantly lower untreated LDL-C levels (640.0 ± 155.6 mg/dL [16.6 ± 4.0 mmol/L] vs 506.9 ± 130.1 mg/dL [13.1 ± 3.4 mmol/L], P = .026] and showed a superior response to lipid-lowering therapy (LLT), with a greater percentage (70.6% ± 12.0%) reduction in LDL-C levels (P = .015). While xanthomas were present in 62.5% of LDLR variant patients, they were less frequent (42.9%) in the LDLRAP1 group (P = .107). Cardiovascular complications were observed exclusively in LDLR variant patients. Fourteen patients required lipoprotein apheresis (LA), and one underwent liver transplantation due to severe aortic stenosis. CONCLUSION: This study highlights the importance of genetic testing in differentiating classical semidominant homozygous FH from ARH, given their phenotypic overlap but distinct treatment responses. LDLRAP1 variant patients with ARH exhibit better LDL-C reductions with conventional LLT, suggesting a milder phenotype. Early diagnosis, aggressive LLT, and novel treatments are essential to mitigate cardiovascular risk. Future studies with larger cohorts and long-term follow-ups are needed to refine treatment strategies for pediatric FH.

Humans↗
PubMed1994

Mapping of the gene for autosomal recessive polycystic kidney disease (ARPKD) to chromosome 6p21-cen.

Autosomal recessive polycystic kidney disease (ARPKD) is one of the major hereditary nephropathies in children predominantly presenting in early childhood. The clinical picture is variable but there is a fatal outcome in many cases. We have performed linkage analysis in 16 ARPKD families and localized the ARPKD gene to chromosomal region 6p21-cen with no evidence for genetic heterogeneity among different clinical phenotypes. Linkage was confirmed using six adjacent microsatellite markers and the highest lod score of 7.42 was obtained with D6S272 at theta = 0.00. Our findings should lead to more accurate forms of prenatal diagnosis than those currently available using ultrasound.

Base Sequence↗
PubMed2024

THBS1 is a new autosomal recessive non-syndromic hearing impairment gene.

BACKGROUND: Prelingual hearing impairment (HI) is genetically highly heterogenous. Early diagnosis and intervention are essential for psychosocial development. In this study we investigated a consanguineous family from Pakistan with autosomal recessive (AR) non-syndromic sensorineural HI (NSHI). METHODS: A DNA sample from an HI member of a consanguineous Pakistani family segregating ARNSHL underwent exome sequencing. Using Sanger sequencing select variants were validated and tested for segregation using DNA samples from additional family members. We further investigated RNA expression data for the candidate gene in mouse and human inner ear and human inner ear organoids using data obtained from the gene Expression Analysis Resource. RESULTS: We identified thrombospondin 1 (THBS1) as a new NSHI gene. A homozygous frameshift variant [c.1470del: p.(Ile491Serfs*45)] was observed in the three hearing-impaired and in the heterozygous state in three unaffected family members. Unlike for most ARNSHI, hearing-impaired individuals had audiograms with a sloping pattern, showing more pronounced HI in the mid and high frequencies (ranging from moderate to profound) compared to the low frequencies. RNA expression data indicates THBS1 is expressed during human inner ear development. Additionally, THBS1 is expressed in the cochlear epithelium and supporting cells of the mouse inner ear during embryonic and postnatal stages. Previously, THBS1 was demonstrated to affect hearing in knockout mice by influencing the formation and function of afferent synapses in the inner ear. CONCLUSIONS: Our findings highlight THBS1 as a potential novel candidate gene for human HI characterized by a sloping high-frequency audio profile. This discovery enhances our understanding of the genetic etiology of HI and will aid in advancing molecular diagnosis.

Humans↗
PubMed2025

Genetic analysis of three patients from two unrelated Chinese families with autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare early-onset neurodegenerative disorder characterized by progressive cerebellar ataxia, spasticity, and sensorimotor peripheral neuropathy. This disorder is caused by homozygous or compound heterozygous variants in the sacsin (SACS) gene on chromosome 13q12.12. Three patients with ARSACS from two unrelated Chinese families were recruited for this study. Patient #1 was an 18-year-old male who had been walking unstably for 12 years. Patient #2, the younger sister of Patient #1, was a 5-year-old girl who had been walking unstably for 2 years. Patient #3 was a 19-year-old female who had been walking unstably and a tendency to fall for 17 years. For Patient #1, whole-exome sequencing (WES) identified a hemizygous variant c.8310_8313delAGAT (p.Asp2771fs4*) in SACS (NM_014363.6), with the father being heterozygous, the mother wild-type, and Patient #2 hemizygous, as verified by Sanger sequencing. Additional copy number variant analysis of the WES data indicated that Patient #1 had a heterozygous gross deletion of chr13q12.12 (chr13:23,808,732 - 24,890,322). Low-coverage whole-genome sequencing results revealed that Patient #2 carried a chr13q12.12 deletion (chr13:23,520,000-24,940,000). Together with Sanger sequencing results, this gross deletion was speculated to have been inherited from the mother, further explaining the hemizygous state of c.8310_8313delAGAT (p.Asp2771fs4*) in Patients #1 and #2. Through WES, Patient #3 was identified as having suspected compound heterozygous variants of c.2881 C > T (p.Arg961*) and c.6409 C > T (p.Gln2137*), inherited from the father and mother, respectively, as confirmed by Sanger sequencing. This study identified three variants in SACS. The c.8310_8313delAGAT (p.Asp2771fs4*) is novel, whereas c.2881 C > T (p.Arg961*) and c.6409 C > T (p.Gln2137*) have been reported previously. Moreover, this study highlights the growing trend that ARSACS has become increasingly prevalent worldwide rather than being localized to a specific region or race. As an increasing number of patients with ARSACS are diagnosed, the genetic spectrum of ARSACS will gradually broaden, providing an accurate genetic basis for prenatal diagnosis of mothers in the years ahead, if possible.

Adolescent↗
PubMed1995

The severe perinatal form of autosomal recessive polycystic kidney disease maps to chromosome 6p21.1-p12: implications for genetic counseling.

Autosomal recessive polycystic kidney disease (ARPKD) is a one of the most common hereditary renal cystic diseases in children. Its clinical spectrum is widely variable with most cases presenting in infancy. Most affected neonates die within the first few hours of life. At present, prenatal diagnosis relies on fetal sonography, which is often imprecise in detecting even the severe form of the disease. Recently, in a cohort of families with mostly milder ARPKD phenotypes, an ARPKD locus was mapped to a 13-cM region of chromosome 6p21-cen. To determine whether severe perinatal ARPKD also maps to chromosome 6p, we have analyzed the segregation of seven microsatellite markers from the ARPKD interval in 22 families with the severe phenotype. In the majority of the affected infants, ARPKD was documented by histopathology. Our data confirm linkage and refine the ARPKD region to a 3.8-cM interval, delimited by the markers D6S465/D6S427/D6S436/D6S272 and D6S466. Taken together, these results suggest that, despite the wide variability in clinical phenotypes, there is a single ARPKD gene. These linkage data and the absence of genetic heterogeneity in all families tested to date have important implications for DNA-based prenatal diagnoses as well as for the isolation of the ARPKD gene.

Amniocentesis↗
PubMed2003

Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene.

BACKGROUND: The first locus for demyelinating autosomal recessive Charcot-Marie-Tooth (ARCMT) disease was identified in 8q13, where mutations in GDAP1 have been found. Mutations in the same gene have been detected in families with axonal ARCMT disease. OBJECTIVE: To determine the clinical, electrophysiologic, and morphologic characteristics of a consanguineous Moroccan family with ARCMT disease associated with the S194X mutation in the GDAP1 gene. METHODS: Four patients from a consanguineous Moroccan family were examined clinically and electrophysiologically. In one patient, a morphometric and ultrastructural study of a peroneal nerve biopsy sample was performed. Mutation in the coding region of the GDAP1 gene was identified by direct sequencing. RESULTS: Neuropathy was evident early in childhood, walking was delayed in one patient, and onset of symptoms occurred before 18 months in the others. The phenotype was severe: foot deformities and disabilities involving the hands and feet developed toward the end of the first decade, followed by involvement of proximal muscles in the lower limbs, leading to loss of autonomy. Electrophysiologic findings were consistent with an axonal form of CMT disease: motor nerve conduction velocities, recordable in one patient only, were greater than 40 m/sec. Sensory nerve action potentials were either abolished or substantially reduced in amplitude. The morphologic data supported the diagnosis of axonal neuropathy, showing a marked reduction in myelinated fibers and signs of axonal regeneration, including frequent pseudo-onion bulb formations. The 4 patients in this family were homozygous for the S194X mutation in the GDAP1 gene. CONCLUSION: Electrophysiologic and pathological findings support the hypothesis of an axonal disorder in this ARCMT family with the S194X mutation in the GDAP1 gene.

Adolescent↗
PubMed1987

Recessive dystrophic epidermolysis bullosa.

Recessive epidermolysis bullosa dystrophica (REBD), a bullous disorder of the skin and mucous membranes, is frequently associated with ocular complications. A 40-year-old woman presented with lid ulcerations, chronic conjunctivitis, diffuse subepithelial corneal scarring, corneal ulceration, and cataracts. Management with intensive lubricant therapy, soft-bandage contact lenses, and cataract extraction successfully restored her sight. Histologic examination via light and electron microscopy revealed blister formation and scarring beneath the epithelial basement membrane of both the skin and cornea, confirming the diagnosis of REBD. The ultrastructure of the skin and cornea and the ocular complications of the major forms of epidermolysis are described herein. To our knowledge, successful ocular management of a confirmed case of REBD with complete ocular histopathologic features has not been documented.

Adult↗
PubMed2004

Severe tracheobronchial stenosis in the X-linked recessive form of chondrodysplasia punctata.

The X-linked recessive form of chondrodysplasia punctata, characterized by chondrodysplasia and punctate calcification of cartilage, is caused by a defect in the vitamin K-dependent enzyme arylsulfatase E. We herein describe a male infant with chondrodysplasia punctata and stenosis and calcification of the entire trachea and main bronchi. To our knowledge, this is the first case of chondrodysplasia punctata reported in the English literature with such extensive airway manifestations.

Bronchial Diseases↗
PubMed1987

Autosomal recessive progressive high-frequency sensorineural deafness in childhood.

Autosomal recessive progressive high-frequency sensorineural deafness in childhood occurred in six patients from two families. This progressive sensorineural hearing loss starts mainly in the higher frequencies. There is an abrupt decline in the audiogram that slowly decreases with the increase of the hearing loss in the lower frequencies.

Adult↗
PubMed1991

Autosomal recessive lethal infantile cytochrome C oxidase deficiency.

Three bedouin children with mitochondrial myopathy due to cytochrome c oxidase deficiency presented with progressive muscle weakness, failure to thrive, proximal renal tubular acidosis, and lactic acidemia leading to death. Two died by age 5 months and one by age 16 months. Cytochrome c oxidase was markedly reduced in skeletal muscle extracts of all three. Three other children of the same family with most probably the same metabolic aberration are also described. We suggest an autosomal recessive inheritance for this lethal mitochondrial myopathy.

Acidosis, Renal Tubular↗