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BMC Medical Genomics May 2024Bosma arhinia microphthalmia syndrome (BAMS; MIM603457) is a rare genetic disorder, predominantly autosomal dominant. It is a multi-system developmental disorder...
BACKGROUND
Bosma arhinia microphthalmia syndrome (BAMS; MIM603457) is a rare genetic disorder, predominantly autosomal dominant. It is a multi-system developmental disorder characterized by severe hypoplasia of the nose and eyes, and reproductive system defects. BAMS is extremely rare in the world and no cases have been reported in Chinese population so far. Pathogenic variants in the SMCHD1 gene (MIM614982) cause BAMS, while the underlying molecular mechanisms requires further investigation.
CASE PRESENTATION
In this study, a Chinese girl who has suffered from congenital absence of nose and microphthalmia was enrolled and subsequently submitted to a comprehensive clinical and genetic evaluation. Whole-exome sequencing (WES) was employed to identify the genetic entity of thisgirl. A heterozygous pathogenic variant, NM_015295, c.1025G > C; p. (Trp342Ser) of SMCHD1 was identified. By performing very detailed physical and genetic examinations, the patient was diagnosed as BAMS.
CONCLUSION
This report is the first description of a variant in SMCHD1 in a Chinese patient affected with BAMS.Our study not only furnished valuable genetic data for counseling of BAMS, but also confirmed the diagnosis of BAMS, which may help the management and prognosis for this patient.
Topics: Humans; Microphthalmos; Female; Chromosomal Proteins, Non-Histone; Choanal Atresia; China; Asian People; Nose; Exome Sequencing; East Asian People
PubMed: 38773541
DOI: 10.1186/s12920-024-01907-6 -
Gaceta Medica de Mexico 2024
Topics: Humans; Microphthalmos; Anophthalmos
PubMed: 38753555
DOI: 10.24875/GMM.M24000852 -
Oman Journal of Ophthalmology 2024
PubMed: 38524315
DOI: 10.4103/ojo.ojo_229_22 -
Investigative Ophthalmology & Visual... Mar 2024A molecular diagnosis is only made in a subset of individuals with nonisolated microphthalmia, anophthalmia, and coloboma (MAC). This may be due to underutilization of...
PURPOSE
A molecular diagnosis is only made in a subset of individuals with nonisolated microphthalmia, anophthalmia, and coloboma (MAC). This may be due to underutilization of clinical (whole) exome sequencing (cES) and an incomplete understanding of the genes that cause MAC. The purpose of this study is to determine the efficacy of cES in cases of nonisolated MAC and to identify new MAC phenotypic expansions.
METHODS
We determined the efficacy of cES in 189 individuals with nonisolated MAC. We then used cES data, a validated machine learning algorithm, and previously published expression data, case reports, and animal models to determine which candidate genes were most likely to contribute to the development of MAC.
RESULTS
We found the efficacy of cES in nonisolated MAC to be between 32.3% (61/189) and 48.1% (91/189). Most genes affected in our cohort were not among genes currently screened in clinically available ophthalmologic gene panels. A subset of the genes implicated in our cohort had not been clearly associated with MAC. Our analyses revealed sufficient evidence to support low-penetrance MAC phenotypic expansions involving nine of these human disease genes.
CONCLUSIONS
We conclude that cES is an effective means of identifying a molecular diagnosis in individuals with nonisolated MAC and may identify putatively damaging variants that would be missed if only a clinically available ophthalmologic gene panel was obtained. Our data also suggest that deleterious variants in BRCA2, BRIP1, KAT6A, KAT6B, NSF, RAC1, SMARCA4, SMC1A, and TUBA1A can contribute to the development of MAC.
Topics: Animals; Humans; Anophthalmos; Coloboma; Exome Sequencing; Microphthalmos; Algorithms; DNA Helicases; Nuclear Proteins; Transcription Factors; Histone Acetyltransferases
PubMed: 38502138
DOI: 10.1167/iovs.65.3.25 -
International Journal of Molecular... Feb 2024Ocular malformations (OMs) arise from early defects during embryonic eye development. Despite the identification of over 100 genes linked to this heterogeneous group of...
Ocular malformations (OMs) arise from early defects during embryonic eye development. Despite the identification of over 100 genes linked to this heterogeneous group of disorders, the genetic cause remains unknown for half of the individuals following Whole-Exome Sequencing. Diagnosis procedures are further hampered by the difficulty of studying samples from clinically relevant tissue, which is one of the main obstacles in OMs. Whole-Genome Sequencing (WGS) to screen for non-coding regions and structural variants may unveil new diagnoses for OM individuals. In this study, we report a patient exhibiting a syndromic OM with a de novo 3.15 Mb inversion in the 6p25 region identified by WGS. This balanced structural variant was located 100 kb away from the gene, previously associated with ocular defects in the literature. We hypothesized that the inversion disrupts the topologically associating domain of and impairs the expression of the gene. Using a new type of samples to study transcripts, we were able to show that the patient presented monoallelic expression of in conjunctival cells, consistent with the abolition of the expression of the inverted allele. This report underscores the importance of investigating structural variants, even in non-coding regions, in individuals affected by ocular malformations.
Topics: Humans; Transcription Factors; Microphthalmos; Anterior Eye Segment; Eye Abnormalities; Alleles; Forkhead Transcription Factors; Mutation
PubMed: 38473917
DOI: 10.3390/ijms25052669 -
Cureus Feb 2024Foveal hypoplasia is a retinal disorder characterized by the anatomic absence of the foveal pit. It might be isolated or associated with poor vision and several...
Foveal hypoplasia is a retinal disorder characterized by the anatomic absence of the foveal pit. It might be isolated or associated with poor vision and several conditions such as albinism, aniridia, microphthalmos, congenital nystagmus, or other diseases. Genetic and non-genetic causes can play a role in foveal pit development. However, the exact mechanism that causes foveal pit absence has not been determined. This study reports a five-year-old boy who presented to the eye clinic with bilateral poor vision since birth. Optical coherence tomography (OCT) was performed and confirmed the absence of the foveal pit in both eyes. Diagnosis of foveal hypoplasia was made. The parents reported a positive family history of similar conditions, specifically, a paternal grandfather, a male paternal cousin, and a brother. To the best of our knowledge, this is the first reported case of foveal hypoplasia, with a positive family history in the male gender specifically. Thus, inheritance is presumed to be X-linked recessive. We acknowledge that further investigation by genetic testing would offer further insight into this case.
PubMed: 38465154
DOI: 10.7759/cureus.53891 -
International Journal of Ophthalmology 2024This narrative review aimed to have an algorithmic approach to microphthalmos by a systematic search. The definition can be related to a number of special phenotypes. In... (Review)
Review
This narrative review aimed to have an algorithmic approach to microphthalmos by a systematic search. The definition can be related to a number of special phenotypes. In the more challenging cases of complex microphthalmos, relative anterior microphthalmos, and nanophthalmos, the surgeon can approach these cases more safely if they have a deep understanding of the anatomical variations and ideal formulae for intraocular lens computation and knows how to avoid intra- and post-operative complications. In this article, we review the criteria by which we recognize and describe pre-, intra-, and post-operative considerations, as well as discuss the ideal intraocular lenses for microphthalmos, given the intricate varieties of small eye phenotypes.
PubMed: 38371260
DOI: 10.18240/ijo.2024.02.23 -
Stem Cell Research Mar 2024Retinitis pigmentosa (RP) is the most common retinal degeneration in humans and is characterized by the progressive degeneration of rods and cones and retinal pigment...
Retinitis pigmentosa (RP) is the most common retinal degeneration in humans and is characterized by the progressive degeneration of rods and cones and retinal pigment epithelium. We generated the IOCVi001-A induced pluripotent stem cell (iPSC) line from dermal fibroblast of a patient with a homozygous c.498_499insC (p.(Asn167Glnfs34) variant in the Membrane-type frizzled related protein (MFRP) gene, a genetic defect causing a syndrome characterized by RP and small eye size (nanophthalmos). IOCVi001-A displayed normal stemness, expressed pluripotent stem cell markers and displayed a normal karyotype. This iPSC line can be used for in vitro disease modeling for complex forms of RP.
Topics: Humans; Microphthalmos; Induced Pluripotent Stem Cells; Membrane Proteins; Retinitis Pigmentosa; Mutation; Hypopituitarism
PubMed: 38217995
DOI: 10.1016/j.scr.2024.103309 -
Journal of Medical Case Reports Jan 2024Oculo-facio-cardio-dental (OFCD) syndrome is a rare condition that affects the eyes, face, heart, and teeth of patients. One notable dental characteristic of OFCD is...
BACKGROUND
Oculo-facio-cardio-dental (OFCD) syndrome is a rare condition that affects the eyes, face, heart, and teeth of patients. One notable dental characteristic of OFCD is radiculomegaly, or root gigantism, which highlights the role of dentists in detecting this syndrome. OFCD is an X-linked dominant syndrome that results from a variant in the BCOR gene. Our study presents the first documented case of OFCD in Vietnam and reports a novel BCOR gene variant observed in this case.
CASE PRESENTATION
A 19-year-old Vietnamese female patient with an extremely long root with an abscess was clinically examined for the expression of OFCDs. The radiograph and the variant in BCOR gene were also evaluated. We identified abnormalities in the teeth, as well as ocular, facial, and cardiac features, with radiculomegaly of the canines being a specific symptom for OFCDs. The patient's genetic analysis revealed a pathogenic heterozygous deletion at intron 11 of the BCOR gene, representing a novel variant.
CONCLUSION
Oculo-facio-cardio-dental syndrome (OFCD) is an extremely rare condition characterized by abnormalities in the eyes, face, heart, and teeth, often caused by variants in the BCOR gene. Radiculomegaly, or enlarged dental roots, is a key diagnostic feature of OFCD, and early detection is crucial for preventing future dental complications.
Topics: Female; Humans; Young Adult; Eye Abnormalities; Face; Heart Defects, Congenital; Heart Septal Defects; Microphthalmos; Syndrome
PubMed: 38178193
DOI: 10.1186/s13256-023-04244-x -
European Journal of Medical Genetics Feb 2024Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these...
Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these associated anomalies vary between different studies. The purpose of this investigation was to assess the frequency and the types of associated anomalies among cases with an/microphthalmia in a geographically well defined population of northeastern France of 387,067 consecutive pregnancies from 1979 to 2007. Of the 98 infants with an/microphthalmia born during this period (prevalence at birth of 2.53 per 10,000), 88.8 % had associated anomalies. Cases with associated anomalies were divided into recognizable conditions (25 (25.5%) cases with chromosomal and 17 (17.3%) cases with non chromosomal conditions), and non recognizable conditions (45-45.9%- cases with multiple congenital anomalies -MCA). Trisomy 13 and trisomy 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, oculo-auriculo-vertebral spectrum, CHARGE syndrome and VACTERL association were most often present in recognizable non chromosomal conditions. Anomalies in the musculoskeletal, cardiovascular and central nervous systems were the most common other anomalies in cases with MCA and non recognizable conditions. However, given the limitation of the limited numbers of cases there should be urging caution in interpreting these results. In conclusion the frequency of associated anomalies in infants with anophthalmia and microphthalmia emphasizes the need for a thorough investigation of these cases. Routine screening for other anomalies especially musculoskeletal, cardiac and central nervous systems anomalies may need to be considered in infants with anophthalmia and microphthalmia, and referral of these cases for genetic counselling seems warranty.
Topics: Infant; Infant, Newborn; Pregnancy; Female; Humans; Anophthalmos; Microphthalmos; Heart Defects, Congenital; Limb Deformities, Congenital; CHARGE Syndrome; Prevalence
PubMed: 38110175
DOI: 10.1016/j.ejmg.2023.104892