scholarly journals Hereditary Spherocytosis Caused by a Novel Compound Heterozygous Mutation of the SPTA1 Gene and Autoimmune Hepatitis in a Pediatric Patient

2021 ◽  
Author(s):  
Yu-mei Qin ◽  
Yan-yun Chen ◽  
Lin Liao ◽  
Yang-yang Wu ◽  
Min Chen ◽  
...  
Keyword(s):  
Autoimmune Hepatitis ◽  
Hereditary Spherocytosis ◽  
Clinical Manifestations ◽  
Liver Function Tests ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Concomitant Disease ◽  
Genetic Characteristics ◽  
Paternal Grandmother

Abstract Objective: Patients suffering from both hereditary spherocytosis (HS) and autoimmune hepatitis (AIH) are very rare. We analyzed the clinical and genetic characteristics of a seven-year-old girl with yellow sclerae and abnormal liver function tests, but no further symptoms. Methods: Blood samples were collected from the proband, her parents, and her paternal grandmother, and analyzed using routine laboratory tests, as well as subjected to next-generation and Sanger sequencing.Results: Compound heterozygous mutations of the spectrin alpha, erythrocytic 1 (SPTA1) gene were identified in the proband. Thec.134G>A (p.R45K) and c.6544G>C (p.D2182H) mutations were inherited from her mother and father, respectively. The proband’s father and paternal grandmother had the same mutation. Neither mutation is described in the Human Gene Mutation Database. Conclusions: HS has clinical manifestations similar to AIH, it may be difficult to diagnose when it coexists with AIH. When laboratory results cannot be explained by autoimmune liver disease alone, the possibility of a concomitant disease should be considered. Pedigree investigation and genetic analyses might be required to arrive at the final diagnosis.

scholarly journals Rare novel LPL mutations are associated with neonatal onset lipoprotein lipase (LPL) deficiency in two cases

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yun Qin Wu ◽  
Yue Yuan Hu ◽  
Gui Nan Li
Keyword(s):  
Lipid Metabolism ◽  
Lipoprotein Lipase ◽  
Clinical Manifestations ◽  
Recurrent Infection ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Genetic Characteristics ◽  
Neonatal Onset

Abstract Background Lipoprotein lipase (LPL) deficiency is a monogenic lipid metabolism disorder biochemically characterized by hypertriglyceridemia (HTG) inherited in an autosomal recessive manner. Neonatal onset LPL deficiency is rare. The purpose of this study was to clarify the clinical features of neonatal LPL deficiency and to analyze the genetic characteristics of LPL gene. Methods In order to reach a definite molecular diagnose, metabolic diseases-related genes were sequenced through gene capture and next generation sequencing. Meanwhile, the clinical characteristics and follow-up results of the two newborns were collected and analyzed. Results Three different mutations in the LPL gene were identified in the two newborns including a novel compound heterozygous mutation (c.347G > C and c.472 T > G) and a reported homozygous mutation (c.836 T > G) was identified. Interestingly, both the two neonatal onset LPL deficiency patients presented with suffered recurrent infection in the hyperlipidemia stage, which was not usually found in childhood or adulthood onset LPL deficiency patients. Conclusion The two novel mutaitons, c.347G > C and c.472 T > G, identified in this study were novel, which expanded the LPL gene mutation spectrum. In addition, suffered recurrent infection in the hyperlipidemia stage implied a certain correlation between immune deficiency and lipid metabolism abnormality. This observation further supplemented and expanded the clinical manifestations of LPL deficiency.

scholarly journals Unique three-site compound heterozygous mutation in the WFS1 gene in Wolfram syndrome

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ziyu Ren ◽  
Jixiu Yi ◽  
Min Zhong ◽  
Yunting Wang ◽  
Qicong Liu ◽  
...  
Keyword(s):  
Genetic Disease ◽  
Target Genes ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Wolfram Syndrome ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Compound Heterozygous Mutations ◽  
Wfs1 Gene

Abstract Background Wolfram syndrome (WFS) is a rare autosomal recessive genetic disease whose main cause is mutations in the WFS1 and CISD2 genes. Its characteristic clinical manifestations are diabetes insipidus, diabetes mellitus, optic atrophy and deafness. Methods In this study, two patients from this particular family underwent complete routine biochemical and ophthalmic tests. Blood, urine, routine stool test, visual acuity (VA) examination, visual field assessment, funduscope, optical coherence tomography and periorbital magnetic resonance imaging (MRI) scans were performed for each patient to evaluate whether the nerve fiber layer around the optic nerve head was atrophied and next-generation sequencing of target genes was performed in two patients. Results When the patients were diagnosed with Wolfram syndrome, their genetic analyses suggested unique three-site compound heterozygous mutations (c.2314C > T + c.2194C > T + c.2171C > T) in exon 8 of both patients’ chromosome 4. One mutation (c.2314C > T) was a novel mutation in the known reports of Wolfram syndrome. As a degenerative genetic disease, the types of gene mutations in the Chinese population are generally homozygous mutations at the unit point or compound heterozygous mutations at two nucleotide change sites. However, the two patients reported in this study are the first known cases of compound heterozygous mutations with three mutation sites coexisting on the WFS1 gene in China or even globally. Conclusions This study expands the phenotypic spectrum of Wolfram syndrome and may reveal a novel mutation pattern of pathogenesis of Wolfram syndrome. The implications of this discovery are valuable in the clinical diagnosis, prognosis, and treatment of patients with WFS1.

scholarly journals Novel PTPRQ Mutations Identified in Three Congenital Hearing Loss Patients With Various Types of Hearing Loss

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 184S-192S ◽  
Author(s):  
Naoko Sakuma ◽  
Hideaki Moteki ◽  
Hela Azaiez ◽  
Kevin T. Booth ◽  
Masahiro Takahashi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Clinical Manifestations ◽  
Vestibular Dysfunction ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Caloric Test ◽  
Compound Heterozygous ◽  
Site Mutation ◽  
Vestibular Evoked Myogenic Potential ◽  
Phenotypic Features

Objectives: We present 3 patients with congenital sensorineural hearing loss (SNHL) caused by novel PTPRQ mutations, including clinical manifestations and phenotypic features. Methods: Two hundred twenty (220) Japanese subjects with SNHL from unrelated and nonconsanguineous families were enrolled in the study. Targeted genomic enrichment with massively parallel DNA sequencing of all known nonsyndromic hearing loss genes was performed to identify the genetic cause of hearing loss. Results: Four novel causative PTPRQ mutations were identified in 3 cases. Case 1 had progressive profound SNHL with a homozygous nonsense mutation. Case 2 had nonprogressive profound SNHL with a compound heterozygous mutation (nonsense and missense mutation). Case 3 had nonprogressive moderate SNHL with a compound heterozygous mutation (missense and splice site mutation). Caloric test and vestibular evoked myogenic potential (VEMP) test showed vestibular dysfunction in Case 1. Conclusion: Hearing loss levels and progression among the present cases were varied, and there seem to be no obvious correlations between genotypes and the phenotypic features of their hearing loss. The PTPRQ mutations appeared to be responsible for vestibular dysfunction.

Hepatic Manifestations of 3-Hydroxy-3-Methylglutaryl-Coenzyme-A Lyase Deficiency in Saudi Patients: Experience of a Tertiary Care Center

2020 ◽  
Author(s):  
Sinan Holdar ◽  
Zuhair Rahbeeni ◽  
Khushnooda Ramzan ◽  
Faiqa Imtiaz
Keyword(s):  
Coenzyme A ◽  
Care Center ◽  
Tertiary Care ◽  
Clinical Manifestations ◽  
Research Centre ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Laboratory Findings ◽  
Saudi Patients

Abstract3-Hydroxy-3-methylglutaryl-coenzyme-A lyase (HMGCL) deficiency, a rare autosomal recessive disorder, is caused by a homozygous or compound heterozygous mutation in the HMGCL gene (chromosome 1p36.11). HMGCL catalyzes the final step of leucine degradation and plays a key role in ketone body formation. Several studies have reported general hepatic findings (e.g., hepatomegaly) in patients with HMGCL deficiency, but currently, there are no available data regarding the incidence and epidemiology of liver involvement. The main objective of our study was to investigate the overall clinical manifestations, laboratory findings, genotype, and presence of hepatic involvement in Saudi patients with HMGCL deficiency. A retrospective chart review of patients with HMGCL deficiency including those with a documented hepatic manifestation was performed at the King Faisal Specialist Hospital & Research Centre in Riyadh, Saudi Arabia. We evaluated 50 cases of HMGCL deficiency. Hepatic findings were found in 17 patients at the time of diagnosis. The mean age of hepatic presentation was 135 days, and the median age was 56 days (range: 2–315 days). Hepatomegaly was found in 65%, abnormal biochemical profile in 47%, and an abnormal imaging in 53% of patients. The most frequent mutation in this cohort was the p.Arg41Gln founder mutation (59%). In comparison to data from the current literature, HMGCL deficiency can be considered as a diagnostic metabolite for hepatic manifestations and requires appropriate evaluation, including molecular genetic analysis.

scholarly journals Case Report: White Colored Stool: An Early Sign of Cystic Fibrosis in Infants

2021 ◽  
Vol 9 ◽  
Author(s):  
Jing Guo ◽  
Rong He ◽  
Zhi-qin Mao
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Testing ◽  
Male Infant ◽  
Liver Function Tests ◽  
Compound Heterozygous Mutation ◽  
Sweat Test ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Mutation Site ◽  
Exon 2

A 2-month-old male infant presented with white colored stools 1 month after birth. There was no jaundice of the skin, mucous membrane, or sclera; his liver was enlarged (4 cm below the ribs), and his liver function tests showed slightly elevated total bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA). An abdominal doppler ultrasound showed no signs of biliary atresia. Genetic testing revealed a CFTR hemizygous mutation site (c.223C>T) in exon 3 and exon 2–3 heterozygous deletion mutation. The infant's stool turned yellow after oral administration of pancreatic tablets. Finally, the infant was diagnosed with cystic fibrosis (CF). Review of literature revealed five children (including the infant in this case study) with CF who presented with white stool. All five children had anemia, four had edema and hypoproteinemia, five had changes in stool color (it was pistachio-green color in two patients, pale colored in one, acholic stool in one, and white stool in one), two had cholestasis, one infant had delayed meconium discharge, and three children had delayed growth and hepatomegaly. Two children had an abnormal sweat test, one had a F508del compound heterozygous mutation, and one had three mutation sites (C.214G>G/A, P.A72T; C.650A>A/G, P.E217G, and C.3406G>G/A, P. A1136T), which was a compound heterozygous mutation. So, CF could be included in the differential diagnosis of infants with white stool. Genetic testing could confirm an early diagnosis of CF. Pancreatic replacement therapy has been shown to be beneficial for improving the digestive function.

The genetics and clinical manifestations of patients with vitamin D dependent rickets type 1A

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ayse Ozden ◽  
Hakan Doneray
Keyword(s):  
Vitamin D ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Treatment Modalities ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Laboratory Findings ◽  
Day Range ◽  
The Mean

Abstract Objectives Vitamin D dependent rickets type 1A (VDDR-1A) is a very rare autosomal recessive disorder caused by mutations in the CYP27B1, which encodes vitamin D 1α-hydroxylase. We report the genetics and clinical manifestations of nine patients with VDDR-1A and compare our patients to other cases with the same mutations in the literature. Methods The clinical presentations, clinical and laboratory findings and treatment modalities of the patients were evaluated retrospectively. Results The mean age of the patients at the time of diagnosis was 39.9 months (range: 4.5–111). At the time of diagnosis, six patients had received stoss vitamin D therapy. Clinical findings related to rickets were obvious in seven patients and unclear in two patients. Except for one case, all patients had laboratory findings of rickets. A novel variant and four previously reported mutations in CYP27B1 were identified. The mean calcitriol and elemental calcium dose were 45.5 ng/kg/day (range: 20–70) and 75.6 mg/kg/day (range: 45–125), respectively. Conclusions We found a novel compound heterozygous mutation consisting of a reported duplication [(p.F443Pfs*24 (c.1319_1325 dup CCCACCC)] in exon 8 and a novel deletion [p.D507Efs*34 (c.1521 delC)] in exon 9. Our study suggests that the clinical manifestations and laboratory findings of the patients with VDDR1A are variable even among the patients with the same mutation.

Infantile parkinsonism-dystonia, type 1 (case report)

2020 ◽  
Vol 1 (4) ◽  
pp. 232-241
Author(s):  
Lyudmila M. Kuzenkova ◽  
Lale A. Pak ◽  
Olga B. Kondakova ◽  
Anastasia A. Lyalina ◽  
Polina G. Tsygankova ◽  
...  
Keyword(s):  
Rare Disease ◽  
Dopamine Transporter ◽  
Clinical Manifestations ◽  
Diagnostic Errors ◽  
Synaptic Cleft ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Clinical Diagnoses

Infantile parkinsonism-dystonia, type 1 (DTDS) (OMIM 613135) is a rare inherited autosomal recessive disease that manifests in infancy. The development of the disease is caused by a homozygous or compound-heterozygous mutation in theSLC6A3gene (OMIM 126455), which encodes a dopamine Transporter localized on the short arm of chromosome 5 (5p15). The main pathogenetic mechanism of the disease is the loss of the function of the main dopamine transporter at the presynaptic level, which leads to a decrease in the reuptake of dopamine in the synaptic cleft, depletion of presynaptic dopamine reserves, and an increase in the amount of extraneuronal dopamine. Currently, there are 20 cases of this disease in children in the world. The main clinical manifestations of DTDS are various hyperkinesis patterns (dystonia, chorea, athetosis, etc.), followed by hypokinesia and rigidity, developing against the background of axial hypotension. Difficulties in differential diagnosis lead to the fact that many patients are observed for years with erroneous clinical diagnoses, including cerebral palsy, regularly receiving rehabilitation treatment without clinical effect. The mentioned above explains the need for clinicians to be aware of a rare disease DTDS, which will avoid diagnostic errors, prescribe adequate therapy promptly, and thereby significantly improve the quality of life of patients and their families. The article contains an overview of the etiological, pathogenetic, epidemiological, diagnostic, and therapeutic aspects of DTDS. For the first time in Russia, there is reported a clinical case of this rare disease, which presents the own experience with DTDS patient.

scholarly journals Neonatal Crohn’s disease with Oral ulcer as the first symptom caused by a compound heterozygote mutation in IL-10RA: a case report

Hereditas ◽  
2019 ◽  
Vol 156 (1) ◽  
Author(s):  
Hongyan Lv ◽  
Baojun Qiao ◽  
Liyuan Fang ◽  
Lihong Yang ◽  
Qiuli Wang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Perianal Disease ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Genetic Characteristics ◽  
Oral Ulcers ◽  
Number Of Patients ◽  
Exon 4

Abstract Objective To investigate the clinical and genetic characteristics of neonatal Crohn’s disease (CD), improve recognition of neonatal CD, and reduce the number of patients that are missed or misdiagnosed. Methods A 10-day-old Chinese girl with oral ulcers was admitted to the Department of Neonatology. She later developed a rash and perianal disease, but without diarrhea and stool abnormalities. The patient and her parents underwent next-generation sequencing. Results The results showed that the patient carries a compound heterozygous mutation in the interleukin-10 receptor A (IL-10RA) (NM_001558.3) gene. One heterozygous mutation was c.301 c > T, P. (Arg 101 Trp) in exon 3 of IL-10RA (a missense mutation), and the other was c. 537G > A, P. (Thr 179 =) in exon 4 of IL 10RA (a synonymous mutation). The patient’s father also carries the c.301 c > T, P. (Arg 101 Trp) heterozygous mutation in exon 3 of IL-10RA, whereas her mother carries the c.537G > A, P. (Thr 179 =) heterozygous mutation in exon 4 of IL-10RA. Conclusions The results show that a compound heterozygous mutation in IL-10RA is associated with neonatal CD. Oral ulcers with a rash and perianal disease may be an early symptom of neonatal CD; therefore, such patients should undergo genetic identification as soon as possible.

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