scholarly journals Two Novel Mutations in the SI Gene Associated With Congenital Sucrase-Isomaltase Deficiency: A Case Report in China

2021 ◽  
Vol 9 ◽  
Author(s):  
Jianli Zhou ◽  
Yuzhen Zhao ◽  
Xia Qian ◽  
Yongwei Cheng ◽  
Huabo Cai ◽  
...  
Keyword(s):  
Case Report ◽  
Autosomal Recessive ◽  
Chronic Diarrhea ◽  
Failure To Thrive ◽  
Inherited Disease ◽  
Restricted Diet ◽  
Novel Mutations ◽  
Case Presentation ◽  
Whole Exome ◽  
Novel Variants

Background: Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive inherited disease that leads to the maldigestion of disaccharides and is associated with mutation of the sucrase-isomaltase (SI) gene. Cases of CSID are not very prevalent in China or worldwide but are gradually being identified and reported.Case Presentation: We report a case involving a 14-month-old male who presented with failure to thrive that had begun after food diversification and was admitted for chronic diarrhea. We used a whole-exome sequencing (WES) approach to identify mutations in this patient's genome. WES revealed two novel heterozygous mutations in the SI gene, c.2626C > T (p.Q876*) and c.2872C > T (p.R958C), which were confirmed by Sanger DNA sequencing. With a strict sucrose- and starch-restricted diet, the patient's diarrhea was resolved, and he began to gain weight.Conclusions: We report a case of novel variants in the SI gene that caused CSID. This report provides valuable information for the clinical field, especially in China.

scholarly journals Whole Exome Sequencing Identifies Three Novel Mutations in the ASPM Gene From Saudi Families Leading to Primary Microcephaly

2021 ◽  
Vol 8 ◽  
Author(s):  
Muhammad Imran Naseer ◽  
Angham Abdulrahman Abdulkareem ◽  
Osama Yousef Muthaffar ◽  
Sameera Sogaty ◽  
Hiba Alkhatabi ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Frameshift Mutation ◽  
Genetic Defect ◽  
Deletion Mutation ◽  
Primary Microcephaly ◽  
Novel Mutations ◽  
Whole Exome ◽  
Novel Variants ◽  
Healthy Control

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental defect that is characterized by reduced head circumference at birth along with non-progressive intellectual disability. Till date, 25 genes related to MCPH have been reported so far in humans. The ASPM (abnormal spindle-like, microcephaly-associated) gene is among the most frequently mutated MCPH gene. We studied three different families having primary microcephaly from different regions of Saudi Arabia. Whole exome sequencing (WES) and Sanger sequencing were done to identify the genetic defect. Collectively, three novel variants were identified in the ASPM gene from three different primary microcephaly families. Family 1, showed a deletion mutation leading to a frameshift mutation c.1003del. (p.Val335*) in exon 3 of the ASPM gene and family 2, also showed deletion mutation leading to frameshift mutation c.1047del (p.Gln349Hisfs*18), while in family 3, we identified a missense mutation c.5623A>G leading to a change in protein (p.Lys1875Glu) in exon 18 of the ASPM gene underlying the disorder. The identified respective mutations were ruled out in 100 healthy control samples. In conclusion, we found three novel mutations in the ASPM gene in Saudi families that will help to establish a disease database for specified mutations in Saudi population and will further help to identify strategies to tackle primary microcephaly in the kingdom.

scholarly journals Novel MYO15A Variants are Associated with Hearing Loss in the Two Iranian Pedigrees

2020 ◽  
Author(s):  
somayeh khatami ◽  
Masomeh Askari ◽  
Fatemeh Bahreini ◽  
Morteza Hashemzadeh Chaleshtori ◽  
Saeed Hematian ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Genetic Diagnosis ◽  
Clinical Genetic ◽  
Clinical Evaluations ◽  
Large Size ◽  
Whole Exome ◽  
Novel Variants ◽  
Syndromic Hearing Loss ◽  
Traditional Approaches

Abstract Background: Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods.Methods: This study was a report on two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families. Results: The implementation of WES to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) and its related variants was reported in the present study. Two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 were correspondingly identified and then segregations were confirmed using Sanger sequencing. According to online prediction tools, both identified variants seemed to have damaging effects.Conclusion: This study further supported the effectiveness of WES for genetic diagnosis of ARNSHL as a first approach.

scholarly journals CAPN1 Variants as Cause of Hereditary Spastic Paraplegia Type 76

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Jesus Eduardo Garcia-Berlanga ◽  
Mariana Moscovich ◽  
Isaac Jair Palacios ◽  
Alejandro Banegas-Lagos ◽  
Augusto Rojas-Martinez ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Brain Mri ◽  
Young Female ◽  
Sequencing Analysis ◽  
Spastic Paraplegia ◽  
Case Presentation ◽  
Significant Family History ◽  
Hereditary Spastic Paraplegias ◽  
Whole Exome ◽  
Oculomotor Abnormalities

Background. Autosomal recessive hereditary spastic paraplegias (HSP) are a rare group of hereditary neurodegenerative disorders characterized by spasticity with or without other symptoms. SPG11 gene is the most common cause of autosomal recessive HSP. We report a case of autosomal recessive spastic paraplegia type 76 due to heterozygous variants of CAPN1 in an Argentinean subject. Case Presentation. A 38-year-old Argentinean female presented with progressive gait problems and instability of 15-year duration. Oculomotor abnormalities, ataxia, bradykinesia, cervical dystonia, and lower limb pyramidal signs were observed. Brain MRI was unremarkable. Whole-exome sequencing analysis identified two heterozygous variants in CAPN1. Conclusions. Clinicians should screen for CAPN1 mutation in a young female patient without significant family history with a spastic paraplegia syndrome associated with other symptoms.

3-M syndrome – a primordial short stature disorder with novel CUL7 mutation in two Indian patients

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Radha Rama Devi Akella
Keyword(s):  
Short Stature ◽  
Autosomal Recessive ◽  
Genetic Diagnosis ◽  
Autosomal Recessive Disorder ◽  
Missense Variant ◽  
Postnatal Growth ◽  
Compound Heterozygous ◽  
Case Presentation ◽  
Whole Exome ◽  
Heterozygous Variant

Abstract Objective To evaluate the cause of short stature in children. Case presentation Two children with suspected skeletal dysplasia and short stature were evaluated. Conclusions The 3-M syndrome is a primordial growth disorder manifesting severe postnatal growth restriction, skeletal anomalies and prominent fleshy heels. The 3-M syndrome is a genetically heterogeneous disorder and the phenotype is similar. This is a rare autosomal recessive disorder with normal intellect. Two affected children have been identified by whole-exome sequencing. One patient harboured a compound heterozygous variant and the other was a homozygous missense variant. The genetic diagnosis helped in counselling the families and facilitated prenatal diagnosis in one (case 1) family.

Sanjad-Sakati syndrome with macrocytic anemia and failure to thrive: a case from South Jordan

2018 ◽  
Vol 31 (5) ◽  
pp. 581-584
Author(s):  
Salma A. Ajarmeh ◽  
Eyad M. Al Tamimi
Keyword(s):  
Autosomal Recessive ◽  
Macrocytic Anemia ◽  
Failure To Thrive ◽  
Cow Milk ◽  
Folic Acid Deficiency ◽  
Case Presentation ◽  
Acid Deficiency ◽  
Characteristic Features ◽  
Severe Growth ◽  
Rare Autosomal Recessive Disease

Abstract Backgorund: Sanjad-Sakati syndrome (SSS) is a rare autosomal recessive disease caused by a deletion mutation (155–166del) in exon 3 of the TBCE gene on chromosome 1q42-43. The syndrome is characterized by primary hypoparathyroidism, typical dysmorphic features and severe growth retardation. Case presentation: We encountered a 2-year-old boy with hypocalcemia, failure to thrive and macrocytic anemia. The patient had the characteristic features of SSS and genetic testing confirmed that he was homozygous for the TBCE mutation. Although malabsorption was initially considered the cause of his symptoms, the results did not confirm that diagnosis. Our patient had cow milk protein allergy and folic acid deficiency, which has not been described in previous SSS cases. It was difficult to treat the patient’s hyperphosphatemia and we ultimately selected sevelamer treatment, which was tolerated well and improved his hypocalcemia. Conclusions: SSS should be considered in the differential diagnosis of any infant with hypocalcemia, dysmorphism and failure to thrive.

scholarly journals Ataxia and hypogonadotropic hypogonadism with intrafamilial variability caused by RNF216 mutation

2016 ◽  
Vol 8 (2) ◽  
Author(s):  
Mohammed Alqwaifly ◽  
Saeed Bohlega
Keyword(s):  
Splice Site ◽  
Autosomal Recessive ◽  
Hypogonadotropic Hypogonadism ◽  
Distinct Phenotype ◽  
Splicing Variant ◽  
Autosomal Recessive Cerebellar Ataxia ◽  
Whole Exome ◽  
Novel Variants ◽  
Intrafamilial Variability

Gordon Holmes syndrome (GHS) is a distinct phenotype of autosomal recessive cerebellar ataxia, characterized by ataxia, dementia, reproductive defects and hypogonadism; it has been recently found to be associated with <em>RNF216</em> mutation. We performed whole-exome sequencing and filtered the resulting novel variants by the coordinates of the shared autozygome. We identified a novel splicing variant in <em>RNF216</em> that is likely to abolish the canonical splice site at the junction of exon/intron 13 (NM_207111.3:c.2061G&gt;A). We herein report two patients with GHS caused by a novel <em>RNF216</em> mutation as the first follow up report on <em>RNF216</em>-related GHS, and <em>show</em> interfamilial variability of phenotype supporting the previously reported RNF216-related cases.

scholarly journals Report of Two Novel Mutations in Indian Patients with Rothmund–Thomson Syndrome

2019 ◽  
Vol 08 (03) ◽  
pp. 163-167
Author(s):  
Sakshi Yadav ◽  
Seema Thakur ◽  
Juergen Kohlhase ◽  
Neetu Bhari ◽  
Madhulika Kabra ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Supportive Therapy ◽  
Failure To Thrive ◽  
Autosomal Recessive Disorder ◽  
Skin Lesions ◽  
Poor Growth ◽  
Pathogenic Variants ◽  
Specific Distribution ◽  
Novel Variants ◽  
Rothmund Thomson Syndrome

AbstractRothmund–Thomson syndrome (RTS) is a rare autosomal recessive disorder caused by mutations in RECQL4 and has characteristic clinical features. We report two unrelated phenotypically diverse patients (cases 1 and 2) with RTS having novel variants in RECQL4 gene. Case-1 was evaluated for poor growth and recurrent fractures and skin lesions. Case-2 presented at 4 months with failure to thrive and radial ray defect and developed poikilodermatous skin lesions after infancy. Both cases were confirmed to have homozygous pathogenic variants in RECQL4. Both patients have normal intellect and are on supportive therapy. The presence of characteristic poikiloderma lesions with specific distribution and skeletal anomalies in a patient with proportionate short stature is a clue toward the diagnosis of RTS.

scholarly journals Novel variants identified in CKAP2L in two siblings with Filippi Syndrome

2021 ◽  
pp. mcs.a006130
Author(s):  
Ryan J Patrick ◽  
Jill M Weimer ◽  
Laura Davis-Keppen ◽  
Megan L Landsverk
Keyword(s):  
Intellectual Disability ◽  
Autosomal Recessive ◽  
Missense Variant ◽  
Facial Features ◽  
Loss Of Function ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
The Family ◽  
Novel Variants ◽  
In Trans

Pathogenic variants in CKAP2L have previously been reported in Filippi Syndrome (FS), a rare autosomal recessive, craniodigital syndrome characterized by microcephaly, syndactyly, short stature, intellectual disability, and dysmorphic facial features. To date, fewer than ten patients with pathogenic variants in CKAP2L associated with FS have been reported. All of the previously reported probands have presumed loss-of-function variants (frameshift, canonical splice site, starting methionine) and all but one have been homozygous for a pathogenic variant. Here we describe two brothers who presented with microcephaly, micrognathia, syndactyly, dysmorphic features, and intellectual disability. Whole exome sequencing of the family identified a missense variant, c.2066G>A (p.Arg689His), in trans with a frameshift variant, c.1169_1173del (p.Ile390LysfsTer4), in CKAP2L. To our knowledge, these are the first patients with FS to be reported with a missense variant in CKAP2L and only the second family to be reported with two variants in trans.

scholarly journals Long-term outcome of a patient with Transcobalamin deficiency caused by the homozygous c.1115_1116delCA mutation in TCN2 gene: a case report

2020 ◽  
Author(s):  
Francesco Martino ◽  
Alessandra Magenta ◽  
Maria Letizia Troccoli ◽  
Eliana Martino ◽  
Concetta Torromeo ◽  
...  
Keyword(s):  
Case Report ◽  
Inborn Error ◽  
Autosomal Recessive ◽  
Megaloblastic Anemia ◽  
Clinical Syndrome ◽  
Full Blood Count ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Case Presentation

Abstract Background: Transcobalamin deficiency is a rare autosomal recessive inborn error of cobalamin transport (prevalence: <1/1000000) which clinically manifests in early infancy. Case presentation:We describe the case of a 30 year old woman who at the age of 30 days presented with the classical clinical and laboratory signs of an inborn error of vitamin B12 metabolism. Family history revealed a sister who died at the age of 3 months with a similar clinical syndrome and with pancytopenia. She was started on empirical intramuscular (IM) cobalamin supplements (injections of hydroxocobalamin 1 mg/day for 1 week and then 1 mg twice a week) and several transfusions of washed and concentrated red blood cells.With these treatments a clear improvement in symptoms was observed, with the disappearance of vomiting, diarrhea and normalization of the full blood count. At 8 years of age injections were stopped for 3 months causing the reappearance of megaloblastic anemia. IM hydroxocobalamin was then restarted sine die. The definitive diagnosis could only be established at 29 years of age when a genetic evaluation revealed the homozygous c.1115_1116delCA mutation of TCN2 gene (p.Q373GfsX38).Currently she is a 30-year old healthy lady taking 1 mg of IM hydroxocobalamin once a week.Conclusions: Our case report highlights that early detection of TC deficiency and early initiation of aggressive IM treatment is likely associated with disease control and an overall favorable outcome.

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