The PTRHD1 Mutation in Intellectual Disability

Background: Intellectual disability (ID) is a heterogonous disorder with complex etiology. The frequency of autosomal recessive inheritance defects was elevated in a consanguineous family. Methods: In this study, high-throughput DNA sequencing was performed in an Iranian consanguineous family with two affected individuals to find potential causative variants. Whole-exome sequencing was carried out on the proband and Sanger sequencing was implemented for validation of the likely causative variant in the family members. Results: A novel homozygous missense mutation (p.Arg122Trp) was detected in the PTRHD1 gene. Conclusion: PTRHD1 has been recently introduced as a candidate ID and Parkinsonism causing gene. Our findings are in agreement with the clinical spectrum of PTRHD1 mutations; however, our affected individuals suffer from ID manifestations.

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Whole Exome Sequencing of Six Chinese Families With Hereditary Non-Syndromic Hearing Loss: A Genetic Etiology Study

10.21203/rs.3.rs-132767/v1 ◽

2020 ◽

Author(s):

Pengfei Liang ◽

Fengping Chen ◽

Shujuan Wang ◽

Qiong Li ◽

Wei Li ◽

...

Keyword(s):

Hearing Loss ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Sanger Sequencing ◽

Large Scale ◽

Autosomal Recessive ◽

Autosomal Recessive Inheritance ◽

Chinese Families ◽

Whole Exome ◽

Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results: Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

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Knobloch syndrome in a large Brazilian consanguineous family: Confirmation of autosomal recessive inheritance

American Journal of Medical Genetics ◽

10.1002/ajmg.1320520209 ◽

1994 ◽

Vol 52 (2) ◽

pp. 170-173 ◽

Cited By ~ 27

Author(s):

M. Rita Passos-Bueno ◽

Suely K. Marie ◽

Mario Monteiro ◽

Isaac Neustein ◽

Martin R. Whittle ◽

...

Keyword(s):

Autosomal Recessive ◽

Autosomal Recessive Inheritance ◽

Recessive Inheritance ◽

Consanguineous Family ◽

Knobloch Syndrome

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Novel variants identified in CKAP2L in two siblings with Filippi Syndrome

Molecular Case Studies ◽

10.1101/mcs.a006130 ◽

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.

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Identification of a Novel Homozygous Missense (c.443A>T:p.N148I) Mutation in BBS2 in a Kashmiri Family with Bardet-Biedl Syndrome

BioMed Research International ◽

10.1155/2021/6626015 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Ghazanfar Ali ◽

Sadia ◽

Jia Nee Foo ◽

Abdul Nasir ◽

Chu-Hua Chang ◽

...

Keyword(s):

Sanger Sequencing ◽

Autosomal Recessive ◽

Autosomal Recessive Inheritance ◽

Clinical Feature ◽

Illumina Hiseq ◽

Genetic Studies ◽

Bardet Biedl Syndrome ◽

Whole Exome ◽

Kashmiri Population ◽

Renal Abnormalities

Background. Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease-causing variant/s in patients exhibiting clinical features of BBS. Methods. The identification of disease-causing variant was done by using whole exome sequencing on Illumina HiSeq 4000 platform involving the SeqCap EZ Exome v3 kit (Roche NimbleGen). The identified variant was further validated by Sanger sequencing. Results. WES revealed a novel homozygous missense mutation (NM_031885: c.443A>T:p.N148I) in exon 3 of the BBS2 gene. Sanger sequencing confirmed this variant as homozygous in both affected subjects and heterozygous in obligate parents, demonstrating autosomal recessive inheritance pattern. To the best of our knowledge, this variant was not present in literature and all publically available databases. The candidate variant is predicted to be pathogenic by a set of in-silico softwares. Conclusion. Clinical and genetic spectrum of BBS and BBS-like disorders is not completely defined in the Pakistani as well as in Kashmiri population. Therefore, more comprehensive genetic studies are required to gain insights into genotype-phenotype associations to facilitate carrier screening and genetic counseling of families with such disorders.

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Whole Exome Sequencing of Six Chinese Families with Hereditary Non-syndromic Hearing Loss

10.21203/rs.3.rs-294215/v1 ◽

2021 ◽

Author(s):

Pengfei Liang ◽

Fengping Chen ◽

Shujuan Wang ◽

Qiong Li ◽

Wei Li ◽

...

Keyword(s):

Hearing Loss ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Sanger Sequencing ◽

Large Scale ◽

Autosomal Recessive ◽

Autosomal Recessive Inheritance ◽

Chinese Families ◽

Whole Exome ◽

Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results:Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions:Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

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PROGRESSIVE PIGMENTATION OF WHOLE BODY MIMICKING HEREDITARY RETICULATE PIGMENTATION IN A YOUNG GIRL: A RARE PRESENTATION OF AMYLOID CUTIS DYSCHROMICA

10.36106/ijsr/5611459 ◽

2020 ◽

pp. 1-2

Author(s):

Amarbir Singh Boparai ◽

BK Brar ◽

Narvinderjeet Kaur

Keyword(s):

Autosomal Recessive ◽

Case Reports ◽

Autosomal Recessive Inheritance ◽

Chief Complaint ◽

Whole Body ◽

Recessive Inheritance ◽

Rare Presentation ◽

Systemic Involvement ◽

The Family ◽

Progressive Disorder

Primary cutaneous amyloidosis is a chronic, progressive disorder of skin, because of the amyloid deposition in the skin with no systemic involvement. Amyloid cutis dyschromica (ACD) is considered a rare variant of primary cutaneous amyloidosis with around 50 cases reported so far. Most cases are reported from Asia, majority having the family history. Autosomal recessive inheritance in GPNMB encoding glycoprotein non metastatic gene B has been reported in many cases with few case reports of semidominat inheritance. It is usually asymptomatic condition as opposed to other types of primary cutaneous amyloidosis like macular or lichenoid variant which are associated with moderate to severe pruritus and photosensitvity. Chief complaint in majority of cases is cosmetic concern only. In view of the very few cases reported from India, we hereby report the case of a 28 years old female having similar dyspigmentation in one sibling.

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Pelizaeus Merzbacher phenotype with epilepsy and autosomal recessive inheritance in two siblings

Neuropediatrics ◽

10.1055/s-2006-953589 ◽

2006 ◽

Vol 37 (03) ◽

Author(s):

U Gaiser ◽

J Neuberger ◽

E Regel ◽

R Emmert ◽

M Ries

Keyword(s):

Autosomal Recessive ◽

Autosomal Recessive Inheritance ◽

Recessive Inheritance

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TYPICAL CASES OF ISOLATED GROWTH HORMONE DEFICIENCY WITH AUTOSOMAL RECESSIVE INHERITANCE

Acta Endocrinologica ◽

10.1530/acta.0.0630618 ◽

1970 ◽

Vol 63 (4) ◽

pp. 618-624 ◽

Cited By ~ 5

Author(s):

Y. Kumahara ◽

Y. Okada ◽

K. Miyai ◽

H. Iwatsubo

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Autosomal Recessive ◽

Autosomal Recessive Inheritance ◽

Adult Subject ◽

Hormone Deficiency ◽

Recessive Inheritance ◽

Arginine Infusion ◽

Isolated Growth Hormone Deficiency ◽

Male Dwarf

ABSTRACT A 25-year-old male dwarf and his sister, a 31-year-old woman were investigated. Their respective heights were 114 and 97 cm with proportional statures. Their bone ages were that found in the adult subject. Thyroid functions and metyrapone test were normal and the total urinary gonadotrophin was determined in both cases. HGH secretion was not stimulated by insulin-induced hypoglycaemia, arginine infusion or exercise. Their parents and six other siblings were normal in height. The two patients were therefore assumed to be suffering from an isolated growth hormone deficiency with autosomal recessive inheritance.

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Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14

Current Molecular Medicine ◽

10.2174/1566524019666190730095630 ◽

2019 ◽

Vol 19 (9) ◽

pp. 683-687 ◽

Cited By ~ 3

Author(s):

Tawfiq Froukh ◽

Ammar Hawwari

Keyword(s):

Strong Evidence ◽

Autosomal Recessive ◽

Eye Diseases ◽

Initial Reaction ◽

Genetic Contribution ◽

Loss Of Function ◽

Consanguineous Family ◽

Truncated Protein ◽

Threonine Residue ◽

Whole Exome

Background: Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical. Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases. Methods: In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family. The Homozygous frameshift variant NM_001253826.1:c.60delC;p.Leu21Cysfs*6 was identified in the gene Nacetylgalactosaminyltransferase 14 (GALNT14). The variant does not exist in all public databases neither in our internal exome database. Moreover, no database harbours homozygous loss of function variants in the candidate gene. Result: GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins. Conclusion: As alterations of mucin’s glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.

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