1.A Case of Antley-Bixler Syndrome With a Novel Likely Pathogenic Variant (c.529G>C) in the POR Gene.
Jongwon OH ; Ju Sun SONG ; Jong Eun PARK ; Shin Yi JANG ; Chang Seok KI ; Duk Kyung KIM
Annals of Laboratory Medicine 2017;37(6):559-562
No abstract available.
Antley-Bixler Syndrome Phenotype*
2.Clinical feature and genetic analysis of a family affected by congenital bile acid synthesis defect type 2: identification of 2 novel mutations in AKR1D1 gene.
Ying CHENG ; Li GUO ; Mei DENG ; Yuan-Zong SONG
Chinese Journal of Contemporary Pediatrics 2017;19(7):734-740
Congenital bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive disorder caused by biallelic mutations of AKR1D1 gene, which encodes the Δ4-3-oxo-steroid 5β-reductase. Cholestatic jaundice is the main clinical manifestation, accompanied by malabsorption of fat and fat-soluble vitamins. This paper reported the clinical and genetic features of a CBAS2 patient definitely diagnosed by AKR1D1 genetic analysis. An 8-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 7 months. On physical examination, growth retardation and malnutrition were discovered besides mild jaundice of the skin and sclera. The liver was palpable 8 cm below the right subcostal margin with medium texture, and the spleen was not enlarged. On liver function test, elevated levels of bilirubin (predominantly conjugated bilirubin) and transaminases were detected, but serum total bile acids and γ-glutamyl transpeptidase levels were within the normal ranges. Liver histopathologic analysis showed disorganized bile ducts, obvious multinucleated giant cells, significant cholestasis in hepatocytes, together with portal and interstitial fibrosis and lymphocytic infiltration. Via next generation sequencing analysis and Sanger sequencing confirmation, the infant proved to be a compound heterozygote of the AKR1D1 variants c.579+2delT and c.853C>T(p.Q285X), two novel mutations originated from his mother and father, respectively. CBAS2 was thus definitely diagnosed, and chenodeoxycholic acid was given orally. As a result, the abnormal liver function and hepatomegaly were improved gradually. On a follow-up 3 months later, a soft liver was palpable 2.5 cm below the right subcostal margin, and all liver function indices recovered to normal ranges.
Bile Acids and Salts
;
blood
;
Cholestasis
;
blood
;
genetics
;
physiopathology
;
therapy
;
Humans
;
Infant
;
Liver
;
physiopathology
;
Male
;
Mutation
;
Oxidoreductases
;
blood
;
deficiency
;
genetics
;
Steroid Metabolism, Inborn Errors
;
blood
;
genetics
;
physiopathology
;
therapy
3.Identification of a novel variant of SRD5A2 gene in a child featuring steroid 5α-reductase type 2 deficiency.
Mali LI ; Fengyu CHE ; Shichao QIU ; Zhihua WANG
Chinese Journal of Medical Genetics 2021;38(12):1233-1236
OBJECTIVE:
To explore the clinical characteristics and genetic basis of a child with 5α-reductase type 2 deficiency.
METHODS:
Clinical data of the child was retrospectively analyzed. Targeted capture-next generation sequencing and Sanger sequencing were carried out to detect potential variants.
RESULTS:
The patient's main features included micropenis and hypospadia. He was found to harbor compound heterozygous c.680G>A (p.R227Q) and c.3G>T (p.M1I) variants of the SRD5A2 gene. Among these, c.680G>A (p.R227Q) was inherited from his father and was a known pathogenic mutation, while c.3G>T (p.M1I) was inherited from his mother and was unreported previously.
CONCLUSION
The compound heterozygous variants of the SRD5A2 gene probably underlay the disease in this child, who was eventually diagnosed with 5α-reductase 2 deficiency.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics*
;
Child
;
Disorder of Sex Development, 46,XY
;
Female
;
Humans
;
Hypospadias
;
Male
;
Membrane Proteins/genetics*
;
Mutation
;
Retrospective Studies
;
Steroid Metabolism, Inborn Errors
;
Steroids
4.Two cases of Antley-Bixler syndrome caused by mutations in different genes, FGFR2 and POR.
Hyewon WOO ; Jung Min KO ; Choong Ho SHIN ; Sei Won YANG
Journal of Genetic Medicine 2016;13(1):31-35
Antley-Bixler syndrome (ABS) is a rare form of syndromic craniosynostosis with additional systemic synostosis, including radiohumeral or radioulnar synostosis. Another characteristic feature of ABS is mid-facial hypoplasia that leads to airway narrowing after birth. ABS is associated with mutations in the FGFR2 and POR genes. Patients with POR mutations present with either skeletal manifestations or congenital adrenal hyperplasia with ambiguous genitalia. We report here two cases of ABS caused by mutations in FGFR2 and POR. Although the patients had craniosynostosis and radiohumeral synostosis in common and cranioplasty was performed in both cases, the male with POR mutations showed an elevated level of 17α-hydroxyprogesterone during newborn screening and was diagnosed with congenital adrenal hyperplasia by adrenocorticotropic hormone stimulation. This patient has been treated with hydrocortisone and fludrocortisone. He had no ambiguous genitalia but had bilateral cryptorchidism. On the other hand, the female with the FGFR2 mutation showed severe clinical manifestations: upper airway narrowing leading to tracheostomy, kyphosis of the cervical spine, and coccyx deformity. ABS shows locus heterogeneity, and mutations in two different genes can cause similar craniofacial and skeletal phenotypes. Because the long-term outcomes and inheritance patterns of the disease differ markedly, depending on the causative mutation, early molecular genetic testing is helpful.
Adrenal Hyperplasia, Congenital
;
Adrenocorticotropic Hormone
;
Antley-Bixler Syndrome Phenotype*
;
Coccyx
;
Congenital Abnormalities
;
Craniosynostoses
;
Cryptorchidism
;
Disorders of Sex Development
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Female
;
Fludrocortisone
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Hand
;
Humans
;
Hydrocortisone
;
Infant, Newborn
;
Inheritance Patterns
;
Kyphosis
;
Male
;
Mass Screening
;
Molecular Biology
;
Parturition
;
Phenotype
;
Population Characteristics
;
Spine
;
Synostosis
;
Tracheostomy
5.A Case of Antley-Bixler Syndrome.
Young Rae KIM ; Kook In PARK ; Choon Sik YOON ; Ran NAMGUNG ; Chul LEE ; Dong Gwan HAN
Journal of the Korean Pediatric Society 1995;38(4):582-585
Antley-Bixler syndrome is a very rare disese of characteristic feature of craniosynostosis, brachycephaly, midface hypoplasia, depressed nasal bridge, radiohumeral synostosis and bowing femur. We presented a case of Antley-Bixtler syndrome with brief review of lituratures.
Antley-Bixler Syndrome Phenotype*
;
Craniosynostoses
;
Femur
;
Synostosis
6.Identification of three novel SRD5A2 mutations in Chinese patients with 5α-reductase 2 deficiency.
Tong CHENG ; Hao WANG ; Bing HAN ; Hui ZHU ; Hai-Jun YAO ; Shuang-Xia ZHAO ; Wen-Jiao ZHU ; Hua-Ling ZHAI ; Fu-Guo CHEN ; Huai-Dong SONG ; Kai-Xiang CHENG ; Yang LIU ; Jie QIAO
Asian Journal of Andrology 2019;21(6):577-581
In this study, we investigated the genetics, clinical features, and therapeutic approach of 14 patients with 5α-reductase deficiency in China. Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5α-reductase type 2 gene (SRD5A2). The 5α-reductase activities of three novel mutations were investigated by mutagenesis and an in vitro transfection assay. Most patients presented with a microphallus, variable degrees of hypospadias, and cryptorchidism. Eight of 14 patients (57.1%) were initially reared as females and changed their social gender from female to male after puberty. Nine mutations were identified in the 14 patients. p.G203S, p.Q6X, and p.R227Q were the most prevalent mutations. Three mutations (p.K35N, p.H162P, and p.Y136X) have not been reported previously. The nonsense mutation p.Y136X abolished enzymatic activity, whereas p.K35N and p.H162P retained partial enzymatic activity. Topical administration of dihydrotestosterone during infancy or early childhood combined with hypospadia repair surgery had good therapeutic results. In conclusion, we expand the mutation profile of SRD5A2 in the Chinese population. A rational clinical approach to this disorder requires early and accurate diagnosis, especially genetic diagnosis.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics*
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Adolescent
;
Adult
;
Asian People/genetics*
;
Child
;
Child, Preschool
;
China
;
Disorder of Sex Development, 46,XY/genetics*
;
Follicle Stimulating Hormone/blood*
;
Genitalia, Male/abnormalities*
;
Humans
;
Hypospadias/genetics*
;
Luteinizing Hormone/blood*
;
Male
;
Membrane Proteins/genetics*
;
Mutation/genetics*
;
Sequence Alignment
;
Steroid Metabolism, Inborn Errors/genetics*
;
Testosterone/blood*
;
Young Adult
7.A Practical Approach to Genetic Hypokalemia.
Shih Hua LIN ; Sung Sen YANG ; Tom CHAU
Electrolytes & Blood Pressure 2010;8(1):38-50
Mutations in genes encoding ion channels, transporters, exchangers, and pumps in human tissues have been increasingly reported to cause hypokalemia. Assessment of history and blood pressure as well as the K+ excretion rate and blood acid-base status can help differentiate between acquired and inherited causes of hypokalemia. Familial periodic paralysis, Andersen's syndrome, congenital chloride-losing diarrhea, and cystic fibrosis are genetic causes of hypokalemia with low urine K+ excretion. With respect to a high rate of K+ excretion associated with faster Na+ disorders (mineralocorticoid excess states), glucoricoid-remediable aldosteronism and congenital adrenal hyperplasia due to either 11beta-hydroxylase and 17alpha-hydroxylase deficiencies in the adrenal gland, and Liddle's syndrome and apparent mineralocorticoid excess in the kidney form the genetic causes. Among slow Cl- disorders (normal blood pressure, low extracellular fluid volume), Bartter's and Gitelman's syndrome are most common with hypochloremic metabolic alkalosis. Renal tubular acidosis caused by mutations in the basolateral Na+/HCO3 - cotransporter (NBC1) in the proximal tubules, apical H+-ATPase pump, and basolateral Cl-/HCO3 - exchanger (anion exchanger 1, AE1) in the distal tubules and carbonic anhydroase II in both are genetic causes with hyperchloremic metabolic acidosis. Further work on genetic causes of hypokalemia will not only provide a much better understanding of the underlying mechanisms, but also set the stage for development of novel therapies in the future.
Acid-Base Equilibrium
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Acidosis
;
Acidosis, Renal Tubular
;
Adrenal Glands
;
Adrenal Hyperplasia, Congenital
;
Aldosterone
;
Alkalosis
;
Blood Pressure
;
Carbon
;
Cystic Fibrosis
;
Diarrhea
;
Extracellular Fluid
;
Humans
;
Hyperaldosteronism
;
Hypokalemia
;
Hypotension
;
Ion Channels
;
Kidney
;
Mineralocorticoid Excess Syndrome, Apparent
;
Paralyses, Familial Periodic
;
Renin
8.Anesthetic management of a neonate with Antley-Bixler syndrome: A case report.
Young Suk KWON ; Jae Keun JO ; Yun Hee LIM ; Jun Heum YON ; Kye Min KIM
Anesthesia and Pain Medicine 2011;6(1):89-92
Antley-Bixler syndrome is a congenital anomaly of multiple bones and cartilage, and this was first reported by Antley and Bixler in 1975. It is characterized by craniosynostosis, midface hypoplasia with choanal stenosis and atresia, radiohumeral synostosis and femoral bowing. This is sometimes accompanied by cardiac, renal, gastrointestinal and genital malformations. The risk of respiratory distress is high in the infants with this syndrome, and this is most commonly caused by choanal stenosis and atresia. Careful anesthetic management is needed for these infants because of the potential risk of a difficult airway and respiratory complications. We report here on our experience with the anesthetic management of a neonate with Antley-Bixler syndrome and we review the relevant literature.
Anesthesia
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Antley-Bixler Syndrome Phenotype
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Cartilage
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Constriction, Pathologic
;
Craniosynostoses
;
Humans
;
Infant
;
Infant, Newborn
;
Synostosis
9.Genetic Syndromes Associated with Craniosynostosis.
Journal of Korean Neurosurgical Society 2016;59(3):187-191
Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures. It leads not only to secondary distortion of skull shape but to various complications including neurologic, ophthalmic and respiratory dysfunction. Craniosynostosis is very heterogeneous in terms of its causes, presentation, and management. Both environmental factors and genetic factors are associated with development of craniosynostosis. Nonsyndromic craniosynostosis accounts for more than 70% of all cases. Syndromic craniosynostosis with a certain genetic cause is more likely to involve multiple sutures or bilateral coronal sutures. FGFR2, FGFR3, FGFR1, TWIST1 and EFNB1 genes are major causative genes of genetic syndromes associated with craniosynostosis. Although most of syndromic craniosynostosis show autosomal dominant inheritance, approximately half of patients are de novo cases. Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, and Antley-Bixler syndrome are related to mutations in FGFR family (especially in FGFR2), and mutations in FGFRs can be overlapped between different syndromes. Saethre-Chotzen syndrome, Muenke syndrome, and craniofrontonasal syndrome are representative disorders showing isolated coronal suture involvement. Compared to the other types of craniosynostosis, single gene mutations can be more frequently detected, in one-third of coronal synostosis patients. Molecular diagnosis can be helpful to provide adequate genetic counseling and guidance for patients with syndromic craniosynostosis.
Acrocephalosyndactylia
;
Antley-Bixler Syndrome Phenotype
;
Cranial Sutures
;
Craniofacial Dysostosis
;
Craniosynostoses*
;
Diagnosis
;
Genetic Counseling
;
Humans
;
Skull
;
Sutures
;
Synostosis
;
Wills
10.A case of Antley-Bixler syndrome caused by novel POR mutations.
Can PENG ; Chengzi HUANG ; Hu TAN ; Lingqian WU
Chinese Journal of Medical Genetics 2019;36(10):1025-1027
OBJECTIVE:
To explore the genetic basis for a child affected with multiple malformations.
METHODS:
Genomic DNA was extracted from peripheral blood samples from the child and her parents. Tro whole exome sequencing and bioinformatics analysis were carried out. Suspicted mutations were verified by PCR and Sanger sequencing.
RESULTS:
The patient, a 2-year-old girl, presented with multiple malformations including dysmorphism, skeletal malformations and ambigulous genitalia. Through genetic testing, she was diagnosed with Antley-Bixler syndrome caused by compound heterozygous mutations of the POR gene (c.919G>T and c.1615G>A), which were derived from her mother and father, respectively.
CONCLUSION
The compound heterozygous mutations of the POR gene probably underlie the Antley-Bixler syndrome in this patient.
Abnormalities, Multiple
;
genetics
;
Antley-Bixler Syndrome Phenotype
;
genetics
;
Child, Preschool
;
Cytochrome P-450 Enzyme System
;
genetics
;
Female
;
Humans
;
Mutation
;
Whole Exome Sequencing