scholarly journals C4OH is a Potential Screening Marker - A Multicenter Retrospective Study of Patients with Beta-Ketothiolase Deficiency in China

2020 ◽  
Author(s):  
Yiming Lin ◽  
Zhantao Yang ◽  
Chiju Yang ◽  
Haili Hu ◽  
Haiyan He ◽  
...  
Keyword(s):  
Chinese Population ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Autosomal Recessive Disorder ◽  
Urinary Organic Acid ◽  
Mutational Spectrum ◽  
Molecular Profiles ◽  
Biallelic Mutations ◽  
Almost All ◽  
Screening Marker

Abstract Background: Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutations in ACAT1 that affects both isoleucine catabolism and ketolysis. Scant information is available regarding the incidence, newborn screening (NBS), and mutational spectrum in China.Methods: We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published Chinese BKTD patients data.Results: Totally 16,088,190 newborns were screened and 14 were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. Twenty-nine patients were genetically diagnosed as BKTD and 12 patients were newly identified. Most patients showed typical blood acylcarnitine and urinary organic acid profiles. In particular, almost all patients (15/16, 94%) showed elevated C4OH levels. Eighteen patients presented acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of 9 patients were triggered by infections, diarrhea, and vaccination. About two thirds of patients have favorable outcomes, one showed developmental delay, while three had died. Twenty-seven distinct variants were identified in ACAT1, among which 5 were found to be novel.Conclusion: This study presented the largest series of BKTD cohort in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by adding C4OH to the current panel of C5OH and C5:1 markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in Chinese population were expanded with 5 newly identified variants.

scholarly journals C4OH is a potential newborn screening marker—a multicenter retrospective study of patients with beta-ketothiolase deficiency in China

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yiming Lin ◽  
Zhantao Yang ◽  
Chiju Yang ◽  
Haili Hu ◽  
Haiyan He ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Autosomal Recessive Disorder ◽  
Published Data ◽  
Urinary Organic Acid ◽  
Biallelic Mutation ◽  
Mutational Spectrum ◽  
Almost All ◽  
Screening Marker

Abstract Background Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutation of ACAT1 that affects both isoleucine catabolism and ketolysis. There is little information available regarding the incidence, newborn screening (NBS), and mutational spectrum of BKTD in China. Results We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published data from Chinese BKTD patients. A total of 16,088,190 newborns were screened and 14 patients were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. In total, twenty-nine patients were genetically diagnosed with BKTD, 12 of which were newly identified. Most patients exhibited typical blood acylcarnitine and urinary organic acid profiles. Interestingly, almost all patients (15/16, 94%) showed elevated 3-hydroxybutyrylcarnitine (C4OH) levels. Eighteen patients presented with acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of nine patients were triggered by infections, diarrhea, or an inflammatory response to vaccination. Approximately two-thirds of patients had favorable outcomes, one showed a developmental delay and three died. Twenty-seven distinct variants were identified in ACAT1, among which five were found to be novel. Conclusion This study presented the largest series of BKTD cohorts in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by the addition of C4OH to the current panel of 3-hydroxyisovalerylcarnitine and tiglylcarnitine markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in the Chinese population were expanded with five newly identified variants.

scholarly journals Case report: two novel VPS13B mutations in a Chinese family with Cohen syndrome and hyperlinear palms

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Sha Zhao ◽  
Zhenqing Luo ◽  
Zhenghui Xiao ◽  
Liping Li ◽  
Rui Zhao ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Chinese Population ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Case Presentation ◽  
Cohen Syndrome ◽  
The Family ◽  
Sporadic Cases

Abstract Background Cohen syndrome (CS) is an uncommon developmental disease with evident clinical heterogeneity. VPS13B is the only gene responsible for CS. Only few sporadic cases of CS have been reported in China. Case presentation A Chinese family with two offspring–patients affected by developmental delay and intellectual disability was investigated in this study. Exome sequencing was performed, and compound heterozygous mutations in VPS13B were segregated for family members with autosomal recessive disorder. Splicing mutation c.3666 + 1G > T (exon 24) and nonsense mutation c. 9844 A > T:p.K3282X (exon 54) were novel. We revisited the family and learned that both patients are affected by microcephaly, developmental delay, neutropenia, and myopia and have a friendly disposition, all of which are consistent with CS phenotypes. We also found that both patients have hyperlinear palms, which their parents do not have. VPS13B mutations reported among the Chinese population were reviewed accordingly. Conclusions This study presents two novel VPS13B mutations in CS. The identification of hyperlinear palms in a family affected by CS expands the phenotype spectrum of CS.

scholarly journals Case Report: Diabetes in Chinese Bloom Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingqun Deng ◽  
Miao Yu ◽  
Ruizhi Jiajue ◽  
Kai Feng ◽  
Xinhua Xiao
Keyword(s):  
Case Report ◽  
Chinese Population ◽  
Autosomal Recessive ◽  
Molecular Mechanisms ◽  
Autosomal Recessive Disorder ◽  
Bloom Syndrome ◽  
Clinical Spectrum ◽  
Sequence Variant ◽  
First Case ◽  
Helicase Gene

Bloom syndrome (BS) is a rare autosomal recessive disorder that causes several endocrine abnormalities. So far, only one BS pedigree, without diabetes, has been reported in the Chinese population. We presented the first case of BS with diabetes in the Chinese population and explored the clinical spectrum associated with endocrine. Possible molecular mechanisms were also investigated. Our study indicated that BS may be one rare cause of diabetes in the Chinese population. We also found a new pathogenic sequence variant in BLM (BLM RecQ like helicase gene)(NM_000057.4) c.692T>G, which may expand the spectrum of BLM variants.

scholarly journals Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency

2007 ◽  
Vol 9 (11) ◽  
pp. 1-23 ◽  
Author(s):  
João Gonçalves ◽  
Ana Friães ◽  
Luís Moura
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Genetic Recombination ◽  
Autosomal Recessive Disorder ◽  
Gene Duplications ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Recent Developments ◽  
21 Hydroxylase Deficiency

AbstractCongenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by defects in one of several steroidogenic enzymes involved in the synthesis of cortisol from cholesterol in the adrenal glands. More than 90% of cases are caused by 21-hydroxylase deficiency, and the severity of the resulting clinical symptoms varies according to the level of 21-hydroxylase activity. 21-Hydroxylase deficiency is usually caused by mutations in theCYP21A2gene, which is located on the RCCX module, a chromosomal region highly prone to genetic recombination events that can result in a wide variety of complex rearrangements, such as gene duplications, gross deletions and gene conversions of variable extensions. Molecular genotyping ofCYP21A2and the RCCX module has proved useful for a more accurate diagnosis of the disease, and prenatal diagnosis. This article summarises the clinical features of 21-hydroxylase deficiency, explains current understanding of the disease at the molecular level, and highlights recent developments, particularly in diagnosis.

scholarly journals A novel mutation in CYP17A1 gene leads to congenital adrenal hyperplasia: A case report

2019 ◽  
Author(s):  
Majid Nazari ◽  
Mohammad Yahya Vahidi Mehrjardi ◽  
Nosrat Neghab ◽  
Mahdi Aghabagheri ◽  
Nasrin Ghasemi
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Homozygous Deletion ◽  
Blood Levels ◽  
Primary Amenorrhea ◽  
Adrenal Hyperplasia ◽  
Lyase Deficiency

Background: Congenital adrenal hyperplasia is a rare autosomal recessive disorder where the mutation in P450 family 17 subfamily A member 1 gene (CYP17A1) is involved in its etiology. The disorder represents itself with low blood levels of estrogens, androgens, and cortisol that generally couples with hypertension, Hypokalemia, sexual primary amenorrhea, infantilism and in affected individuals. Case: In this study, the CYP17A1 gene in a 14-year-old female was examined. The karyotype of the patient was 46, XX, and the analysis of the CYP17A1 gene by Sanger sequencing revealed a novel homozygous deletion c.1052-1054CCT which led to isolated 17,20-lyase deficiency. Conclusion: In conclusion, this study report an in-frame deletion which results in isolated 17, 20-lyase deficiency, and the mutation might be used for diagnosis in other patients with distinctive clinical symptoms.

scholarly journals Novel CUL7 biallelic mutations alter the skeletal phenotype of 3M syndrome

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Nao Takizaki ◽  
Yoshinori Tsurusaki ◽  
Kaoru Katsumata ◽  
Yumi Enomoto ◽  
Hiroaki Murakami ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Neonatal Period ◽  
Autosomal Recessive Disorder ◽  
Facial Features ◽  
Skeletal Changes ◽  
Novel Variants ◽  
Skeletal Phenotype ◽  
Vertebral Bodies ◽  
Biallelic Mutations ◽  
Severe Growth

Abstract3M syndrome is an autosomal recessive disorder characterized by severe growth retardation, distinct facial features, and skeletal changes, including long slender tubular bones and tall vertebral bodies. We report a Japanese patient with 3M syndrome caused by the biallelic novel variants c.1705_1708del and c.1989_1999del of CUL7. Skeletal features were consistent with 3M syndrome in the early neonatal period but became less obvious by 2 years of age.

scholarly journals Novel In-Frame Deletion in HTRA1 Gene, Responsible for Stroke at a Young Age and Dementia—A Case Study

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1955
Author(s):  
Julija Grigaitė ◽  
Kamilė Šiaurytė ◽  
Eglė Audronytė ◽  
Eglė Preikšaitienė ◽  
Birutė Burnytė ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Brain Magnetic Resonance Imaging ◽  
In Silico Analysis ◽  
Magnetic Resonance Imaging Mri ◽  
Biallelic Mutations ◽  
Population Databases ◽  
Autosomal Recessive Manner ◽  
Cerebral Small Vessel Diseases

Biallelic mutations in the high-temperature requirement A serine peptidase 1 (HTRA1) gene are known to cause an extremely rare cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), which belongs to the group of hereditary cerebral small vessel diseases and is mainly observed in the Japanese population. Even though this pathology is inherited in an autosomal recessive manner, recent studies have described symptomatic carriers with heterozygous HTRA1 mutations who have milder symptoms than patients with biallelic HTRA1 mutations. We present the case of a Lithuanian male patient who had a stroke at the age of 36, experienced several transient ischemic attacks, and developed an early onset, progressing dementia. These clinical symptoms were associated with extensive leukoencephalopathy, lacunar infarcts, and microbleeds based on brain magnetic resonance imaging (MRI). A novel heterozygous in-frame HTRA1 gene deletion (NM_002775.5:c.533_535del; NP_002766.1:p.(Lys178del)) was identified by next generation sequencing. The variant was consistent with the patient’s phenotype, which could not be explained by alternative causes, appeared highly deleterious after in silico analysis, and was not reported in the medical literature or population databases to date.

The diagnosis of cystinosis in patients reveals new CTNS gene mutations in the Chinese population

2019 ◽  
Vol 32 (4) ◽  
pp. 375-382
Author(s):  
Xiao-Qiao Li ◽  
Di Wu ◽  
Xue-Jun Liang ◽  
Wen-Jing Li ◽  
Min Liu ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Growth And Development ◽  
Chinese Population ◽  
Autosomal Recessive ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Diagnostic Procedures ◽  
Alternative Therapies ◽  
Novel Mutations ◽  
Chromosome 17P13

Abstract Background Cystinosis is a rare autosomal-recessive disorder caused by a defective transport of cystine across the lysosomal membrane. Previous studies have mapped cystinosis to the CTNS gene which is located on chromosome 17p13, and various CTNS mutations have been identified to correlate them with this disease. Methods We analyzed six patients from five unrelated families who were diagnosed with cystinosis in our hospital. We described the diagnostic procedures for all the patients and proposed alternative therapies for cystinosis patients instead of using cysteamine, an orphan drug which was commercially unavailable in China. Moreover, genetic analysis of all patients’ samples was carried out to identify novel CTNS gene mutations. Results and conclusions The patients in this study were followed up from 1 to more than 10 years to monitor their growth and development, which indicated that the alternative therapies we used were helpful to ameliorate the complications of the cystinosis patients without cysteamine. Furthermore, by sequencing the patients’ genome, we identified novel mutations in the CTNS gene including: c.477C > G (p.S159R), c.274C > T (p.Q92X) and c.680A > T (p.E227V); these mutations were only observed in cystinosis patients and had never been reported in any other populations, suggesting they might be specific to Chinese cystinosis patients.

scholarly journals Phenotypic Variability of MEGF10 Variants Causing Congenital Myopathy: Report of Two Unrelated Patients from a Highly Consanguineous Population

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1783
Author(s):  
Mohammad AlMuhaizea ◽  
Omar Dabbagh ◽  
Hanan AlQudairy ◽  
Aljouhra AlHargan ◽  
Wafa Alotaibi ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Autosomal Recessive ◽  
Phenotypic Variability ◽  
Autosomal Recessive Disorder ◽  
Congenital Myopathy ◽  
Compound Heterozygous ◽  
Congenital Myopathies ◽  
Hereditary Disorders ◽  
Epidermal Growth ◽  
Biallelic Mutations

Congenital myopathies are rare neuromuscular hereditary disorders that manifest at birth or during infancy and usually appear with muscle weakness and hypotonia. One of such disorders, early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD, OMIM: 614399, MIM: 612453), is a rare autosomal recessive disorder caused by biallelic mutations (at homozygous or compound heterozygous status) in MEGF10 (multiple epidermal growth factor-like domains protein family). Here, we report two unrelated patients, who were born to consanguineous parents, having two novel MEGF10 deleterious variants. Interestingly, the presence of MEGF10 associated EMARDD has not been reported in Saudi Arabia, a highly consanguineous population. Moreover, both variants lead to a different phenotypic onset of mild and severe types. Our work expands phenotypic features of the disease and provides an opportunity for genetic counseling to the inflicted families.

Three Cases of Joubert Syndrome in a Consanguineous Syrian Family and a Interesting Case of Multinational Collaboration

2021 ◽  
Author(s):  
Davor Petrović ◽  
Vida Čulić ◽  
Zofia Swinderek-Alsayed
Keyword(s):  
Low Income ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Joubert Syndrome ◽  
Interesting Case ◽  
Low Income Countries ◽  
Ocular Motor ◽  
Quality Health Care ◽  
Quality Health ◽  
Motor Apraxia

AbstractJoubert syndrome (JS) is a rare congenital, autosomal recessive disorder characterized by a distinctive brain malformation, developmental delay, ocular motor apraxia, breathing abnormalities, and high clinical and genetic heterogeneity. We are reporting three siblings with JS from consanguineous parents in Syria. Two of them had the same homozygous c.2172delA (p.Trp725Glyfs*) AHI1 mutation and the third was diagnosed prenatally with magnetic resonance imaging. This pathogenic variant is very rare and described in only a few cases in the literature. Multinational collaboration could be of benefit for the patients from undeveloped, low-income countries that have a low-quality health care system, especially for the diagnosis of rare diseases.

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