Coenzyme Q(10) (CoQ(10)) is a vital lipophilic molecule that transfers electrons from mitochondrial respiratory chain complexes I and II to complex III. Deficiency of CoQ(10) has been associated with diverse clinical phenotypes, but, in most patients, the molecular cause is unknown. The first defect in a CoQ(10) biosynthetic gene, COQ2, ...

The Wiskott-Aldrich syndrome is an X-linked hereditary disorder associated with combined immunodeficiency, thrombocytopenia, small platelets, eczema, and increased susceptibility to autoimmune disorders and cancers. It is caused by mutations in the gene (WAS) for the Wiskott-Aldrich syndrome protein (WASP). We investigated family members of the patients originally described by Wiskott ...

Hyperparathyroidism-jaw tumour (HPT-JT) syndrome is characterized by parathyroid tumours as well as by ossifying fibromas of the mandible and maxilla, renal cysts, or Wilms' tumours. Recently, the gene responsible for HPT-JT syndrome has been identified as the HRPT2 tumour suppressor gene. In an 18-year-old male, a tumour in the maxilla ...

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder that is characterized by branchial cysts or fistulae, external ear malformations and/or preauricular pits, hearing loss and renal anomalies. Recent advances in molecular genetics have shown a human homologue of the Drosophila 'eyes absent' gene (EYA1) on chromosome band 8q13.3 to be ...

Elejalde syndrome (McKusick 200995), also known as acrocephalopolydactylous dysplasia, is a rare condition. We describe a sixth patient with this syndrome which is characterized by craniosynostosis and hyperproliferation of fibroblasts in many tissues including skin, liver, kidney, and pancreas. The cause of the syndrome is the homozygous state of an ...

Noonan syndrome is a relatively common, genetically heterogeneous Mendelian trait with a pleiomorphic phenotype. Prior to the period covered in this review, missense mutations in PTPN11 had been found to account for nearly 50% of Noonan syndrome cases. That gene encodes SHP-2, a protein tyrosine kinase that plays diverse roles ...

AIM: To detail the clinical findings in a British family with molecularly characterised Wagner syndrome. BACKGROUND: Only in the last year has the specific genetic defect in Wagner syndrome been identified, and the background literature of the molecular genetics is outlined. Clinical and laboratory findings in a second case of ...

We report the case of a young boy with fine hair, mild nail dysplasia, blocked nasolacrimal ducts, absence of central incisors, bilateral oligodactyly of feet and anal stenosis. His father showed the same spectrum of anomalies with mild expression. He had mild nail dysplasia, blocked nasolacrimal ducts, inferior dental cysts ...

Pfeiffer syndrome is an autosomal dominant condition classically encompassing both craniosynostosis and digital abnormalities of the hands and feet. Individuals with Pfeiffer syndrome may have mutations within either fibroblast growth factor receptor 1 gene (FGFR1) or FGFR2. FGFR1 mutations often result in less severe craniofacial involvement and hand abnormalities. We ...

Inherited as an autosomal recessive trait, Pendred syndrome is a disease that shows congenital sensorineural hearing loss and goiter, with a positive finding in the perchlorate discharge test. Pendred syndrome results from various mutations in the PDS/SLC26A4 gene that cause production of an abnormal pendrin protein. More than 90 mutations ...

Activating mutations of FGFR3, a negative regulator of bone growth, are well known to cause a variety of short-limbed bone dysplasias and craniosynostosis syndromes. We mapped the locus causing a novel disorder characterized by camptodactyly, tall stature, scoliosis, and hearing loss (CATSHL syndrome) to chromosome 4p. Because this syndrome recapitulated ...

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare, fatal autoimmune disorder caused by mutations in the FOXP3 gene leading to the disruption of signaling pathways involved in regulatory T-lymphocyte function. Lifelong multiagent immunosuppression is necessary to control debilitating autoimmune manifestations such as colitis and food allergies. Allogeneic hematopoietic ...

The clinical combination of anophthalmia/microphthalmia and esophageal atresia was first recognized in 1988 as a distinct variable multi-system malformation syndrome and since then at least 17 cases of the disease have been described, all of them sporadic in occurrence. We report a heterozygous SOX2 gene mutation underlying the syndrome of ...

Fraser syndrome (OMIM 219000) is a rare, autosomal recessive condition with classical features of cryptophthalmos, syndactyly, ambiguous genitalia, laryngeal, and genitourinary malformations, oral clefting and mental retardation. Mutations causing loss of function of the FRAS1 gene have been demonstrated in five patients with Fraser syndrome. However, no phenotype-genotype correlation was ...

Sotos syndrome is an autosomal dominant condition characterised by a distinctive facial appearance, learning disability and overgrowth resulting in tall stature and macrocephaly. In 2002, Sotos syndrome was shown to be caused by mutations and deletions of NSD1, which encodes a histone methyltransferase implicated in chromatin regulation. More recently, the ...

An 80-year-old man was referred to our department for evaluation of repetitive loss of consciousness and faintness with hypokalemia. He had relatively low blood pressure, hypomagnesemia, hypocalciuria and chondrocalcinosis in the knee, clinically suggesting Gitelman's syndrome. A renal clearance study could not be carried out due to the patient's age ...

A Taq I polymorphism, located in intron 4 of the faciogenital dysplasia ( FGD1 ) gene, the gene responsible for Aarskog syndrome, is described. FGD1 encodes a putative Rho/Rac guanine nucleotide exchange factor involved in mammalian morphogenesis. The identification of an intragenic polymorphism will facilitate the accurate carrier detection of ...

Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of ...

Gorlin's syndrome or naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder that predisposes to basal cell carcinomas of the skin, ovarian fibromas, and medulloblastomas. This condition is due to mutations in the Patched (PTCH) gene which maps to chromosome 9q22 and acts as a tumour suppressor gene. ...

We report on a 14 7/12-year-old Japanese female patient with CHARGE syndrome and CHD7 mutation who also exhibited Kallmann syndrome (KS) phenotype. She had poor pubertal development and apparently impaired sense of smell. A GnRH test showed severely compromised responses of LH (<0.5 --> <0.5 IU/L) and FSH (<0.5 --> ...

Gilbert's syndrome (GS) is a benign and inherited state characterized by mild, lifelong, unconjugated hyperbilirubinaemia in the absence of haemolysis or evidence of liver disease. Its molecular basis, mutations in the TATA box upstream of the uridine diphosphoglucose glucuronyltransferase gene, leads to impaired bilirubin glucuronidation. This synopsis outlines the pathophysiology ...

Cutaneous lipoma is rare in children, but it can be part of a syndrome such as the Bannayan-Riley-Ruvalcaba syndrome (BRRS). The BRRS is a dominant autosomal disorder characterized by cutaneous lipomas, macrocephaly, intestinal polyps, and developmental delay associated with PTEN gene mutations. This syndrome is thought to represent a pediatric ...

Odontogenic keratocysts are relatively common lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (or Gorlin syndrome). The PTCH gene has been reported to be associated with Gorlin syndrome. We investigated 10 cases of non-syndromic keratocysts and two other cases associated with Gorlin syndrome, ...

Costello syndrome (CS) is a rare multiple congenital anomaly/mental retardation syndrome characterized by coarse face, loose skin and cardiomyopathy. It is often associated with benign and malignant tumors. Several groups have now demonstrated that CS is caused by recurring mutations in the HRAS gene in different ethnic groups. Here, we ...

Genetic mutations that lead to an accumulation of farnesyl-prelamin A cause progeroid syndromes, including Hutchinson-Gilford progeria syndrome. It seemed possible that the farnesylated form of prelamin A might be toxic to mammalian cells, accounting for all the disease phenotypes that are characteristic of progeria. This concept led to the hypothesis ...

The Wilms tumor suppressor gene, WT1, plays an important role in the development of the urogenital system and the gonads, and clinical syndromes associated with WT1 mutations, such as WAGR syndrome, Denys-Drash syndrome and Frasier syndrome, typically manifest as renal and genitourinary abnormalities. WT1 may also play an important role ...

The WT1 gene encodes a zinc finger transcription factor involved in kidney and gonadal development and, when mutated, in the occurrence of kidney tumor and glomerular diseases. Patients with Denys-Drash syndrome present with early nephrotic syndrome with diffuse mesangial sclerosis progressing rapidly to end-stage renal failure, male pseudohermaphroditism, and Wilms' ...

The term otopalatodigital syndrome spectrum disorders is an umbrella category that includes four phenotypically related conditions, otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick - Needles syndrome. The phenotype of these conditions in the male ranges from a severe perinatally lethal multiple malformation syndrome to a mild skeletal ...

Congenital nephrotic syndrome is clinically and genetically heterogeneous. The majority of cases can be attributed to mutations in the genes NPHS1, NPHS2, and WT1. By homozygosity mapping in a consanguineous family with isolated congenital nephrotic syndrome, we identified a potential candidate region on chromosome 3p. The LAMB2 gene, which was ...

The triple A or Allgrove's syndrome is an autosomal recessive disorder characterized by the triad of achalasia cardia, alacrima and ACTH resistant adrenocortical insufficiency. Mutations of the Achalasia-Addisonianism-Alacrima-Syndrome (AAAS) gene on chromosome 12q13 are associated with this syndrome. We report an Indian family where two siblings were homozygous for a ...

Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (MIM 208085) is an autosomal recessive multisystem disorder that may be associated with germline VPS33B mutations. VPS33B is involved in regulation of vesicular membrane fusion by interacting with SNARE proteins, and evidence of abnormal polarised membrane protein trafficking has been reported in ARC ...

The Cornelia de Lange syndrome is a multiple congenital anomaly syndrome characterised by dysmorphic facial features, hirsutism, severe growth and developmental delays, and malformed upper limbs. The prevalence is estimated to be one per 10,000. Recently, several independent groups proved that Cornelia de Lange syndrome is caused by mutations in ...

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder that is manifested by complement-mediated hemolysis, venous thrombosis, and bone marrow failure and is one disorder of acquired bone marrow failure syndromes that include as aplastic anemia and myelodysplastic syndrome. Nowadays, acquired PNH should be understood as one of the ...

BACKGROUND: Autosomal recessive mutations in deoxyguanosine kinase (DGUOK) have been identified in the hepatocerebral form of mitochondrial DNA (mtDNA) depletion syndrome. OBJECTIVES: To describe the clinical spectrum of DGUOK-related mtDNA depletion syndrome in 6 children and to summarize the literature. RESULTS: We identified pathogenic mutations in DGUOK in 6 children ...

OBJECTIVE: The objective of this study was to characterize the temporal bone phenotype associated with a mutation of GJB2 (encoding connexin 26). STUDY DESIGN: The authors conducted correlative clinical, molecular genetic, and postmortem histopathologic analysis. METHODS: The study subject was a male infant with keratitis-ichthyosis-deafness (KID) syndrome. We performed a ...

An emerging family of extracellular matrix proteins characterized by 12 consecutive CSPG repeats and the presence of Calx-beta motif(s) includes Fras1, QBRICK/Frem1, and Frem2. Mutations in the genes encoding these proteins have been associated with mouse models of Fraser syndrome, which is characterized by subepidermal blistering, cryptophthalmos, syndactyly, and renal ...

Peters Plus syndrome is an autosomal recessive disorder characterized by anterior eye-chamber abnormalities, disproportionate short stature, and developmental delay. After detection of a microdeletion by array-based comparative genomic hybridization, we identified biallelic truncating mutations in the beta 1,3-galactosyltransferase-like gene (B3GALTL) in all 20 tested patients, showing that Peters Plus is ...

Barth syndrome is an X-linked recessive disease caused by mutations in the tafazzin gene. Patients have reduced concentration and altered composition of cardiolipin, the specific mitochondrial phospholipid, and they have variable clinical findings, often including heart failure, myopathy, neutropenia, and growth retardation. This article provides an overview of the molecular ...

Genitopatellar syndrome is a newly described disorder characterized by absent/hypoplastic patellae, lower extremity contractures, urogenital anomalies, dysmorphic features, skeletal anomalies, and agenesis of the corpus callosum. More recently, cardiac anomalies and ectodermal dysplasia have been suggested as additional features of this syndrome. We report on two additional patients with genitopatellar ...

The cardiofaciocutaneous (CFC) syndrome is a condition of sporadic occurrence, with patients showing multiple congenital anomalies and mental retardation. It is characterised by failure to thrive, relative macrocephaly, a distinctive face with prominent forehead, bitemporal constriction, absence of eyebrows, hypertelorism, downward-slanting palpebral fissures often with epicanthic folds, depressed nasal root ...

Even as a rare multiple congenital anomalies/mental retardation syndrome, the C-syndrome (CS, or Opitz C-trigonoecephaly syndrome) is, at long last, beginning to attract attention because of its developmental and causal complexity. Also, the possibility that the apparently balanced translocation recently described in an affected Japanese boy may soon provide a ...

We present a case of Bernard Soulier syndrome in a 9-year-old boy caused by a novel genetic mutation. This child was shown to be homozygous for a single nucleotide deletion (c.1077delG) in the GP1BA gene not previously reported. Clinically, the boy has become refractory to platelet transfusions with both allo-antibodies ...

Type 5 Bartter syndrome has been recently defined as a Bartter syndrome due to the most activating mutations of the calcium-sensing receptor (CaSR). It has been attributed to the inhibition exerted by CaSR activity on sodium transport in the thick ascending limb of the loop of Henle (TALH). Two monozygotic ...

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by the associations of hearing loss, branchial arch defects and renal anomalies. Branchiootic (BO) syndrome is a related disorder that presents without the highly variable characteristic renal anomalies of BOR syndrome. Dominant mutations in the human homologue of the Drosophila eyes ...

BACKGROUND: Larsen syndrome is an autosomal dominant osteochondrodysplasia characterised by large-joint dislocations and craniofacial anomalies. Recently, Larsen syndrome was shown to be caused by missense mutations or small inframe deletions in FLNB, encoding the cytoskeletal protein filamin B. To further delineate the molecular causes of Larsen syndrome, 20 probands with ...

Stickler syndrome is characterized by ophthalmic, articular, orofacial, and auditory manifestations. It has an autosomal dominant inheritance pattern and is caused by mutations in COL2A1, COL11A1, and COL11A2. We describe a family of Moroccan origin that consists of four children with Stickler syndrome, six unaffected children, and two unaffected parents ...

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of ...

Symptomatic West syndrome has heterogeneous backgrounds. Recently, two novel genes, ARX and CDKL5, have been found to be responsible for cryptogenic West syndrome or infantile spasms. Both are located in the human chromosome Xp22 region and are mainly expressed and play roles in fetal brain. Moreover, several genes responsible for ...

Mutations in SALL4, the human homolog of the Drosophila homeotic gene spalt (sal), cause the autosomal dominant disorder known as Okihiro syndrome. In this study, we show that a targeted null mutation in the mouse Sall4 gene leads to lethality during peri-implantation. Growth of the inner cell mass from the ...

Patients with Down syndrome appear to be protected from the development of atherosclerosis. On the contrary, hyperhomocysteinemia is associated with an increased risk for atherosclerosis. As hyperhomocysteinemia due to cystathionine beta synthase deficiency is associated with a decreased expression of paraoxonase-1, a major anti-atherosclerotic component secreted by the liver, we ...