Background. Spastic paraplegia type 4 (SPG4) is the most common type of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. Case Presentation. We report the case of a 27-year-old pregnant Chinese woman with HSP in whom we identified a missense mutation in the SPAST gene (c.1496G&gt;A, p.Arg499His) and a nonsense mutation in the NEFH gene (c.289G&gt;T, p.Glu97<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.04990005pt" id="M1" height="10.1524pt" version="1.1" viewBox="-0.0498162 -10.1025 6.17869 10.1524" width="6.17869pt"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path id="g50-43" d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z"/></g></svg>) via whole-exome sequencing; this finding corroborated that of Sanger sequencing. The patient exhibited the pure SPG4 phenotype with onset during childhood. The SPAST mutation was absent in the parents and paternal relatives. However, the NEFH mutation was identified in five people with no clinical phenotype. Based on theoretical conjecture and the family gene segregation information, we concluded that the SPAST mutation, but not the NEFH mutation, accounted for the proband’s phenotype. Eventually, the woman gave birth to a healthy baby girl with the NEFH mutation. Conclusion. In this report, we identified a missense mutation in the SPAST gene (p.Arg499His) in a 27-year-old pregnant Chinese woman with HSP. We believe that this study expands the knowledge about the clinical parameters and mutation spectrum of SPG4.

Li Xu

Zijuan Peng

Chunhui Zhou

Jiqing Wang

Hunjin Luo

Qin Lu

Zhengjun Bao

A Chinese Patient with Spastic Paraplegia Type 4 with a De Novo Mutation in the SPAST Gene

Background. McCune&#x2013;Albright syndrome (MAS) is a rare heterogeneous genetic disorder that is characterized by a triad of polyostotic fibrous dysplasia (FD), caf&#xe9; au lait spots (CAL), and multiple hyperfunctional endocrinopathies. In general, it is diagnosed clinically. From the triads, two of the findings are enough to make the diagnosis, but genetic testing can be done if it is available. Case Presentation. We report a female child who was symptomatic since the neonatal period with skin hyperpigmentation, breast enlargement, and vaginal bleeding. She was diagnosed with MAS at the age of five years. She had pathological fractures at multiple sites and had raised thyroid hormones since the age of 3&#xbd; years. The child developed severe morbidity as the result of delayed diagnosis and currently became wheelchair dependent. Conclusion. Thorough patient evaluation and appropriate interpretation of findings are crucial steps for timely diagnosis of MAS and better patient care outcomes.

Bereket Fantahun

Seblewongel Desta

Delayed Diagnosis of McCune&#x2013;Albright Syndrome

Mitochondrial DNA (mtDNA) depletion syndromes are a group of autosomal recessive disorders associated with a spectrum of clinical diseases, which include progressive external ophthalmoplegia (PEO). They are caused by variants in nuclear DNA (nDNA) encoded genes, and the gene that encodes for mtDNA polymerase gamma (POLG) is commonly involved. A splice-site mutation in POLG, c.3104+3A &gt; T, was previously identified in three families with findings of PEO, and studies demonstrated this variant to result in skipping of exon 19. Here, we report a 57-year-old female who presented with ophthalmoplegia, ptosis, muscle weakness, and exercise intolerance with a subsequent muscle biopsy demonstrating mitochondrial myopathy on histopathologic evaluation and multiple mtDNA deletions by southern blot analysis. Whole-exome sequencing identified the previously characterized c. 3104+3A &gt; T splice-site mutation in compound heterozygosity with a novel frameshift variant, p.Gly23Serfs<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.04990005pt" id="M1" height="10.1524pt" version="1.1" viewBox="-0.0498162 -10.1025 6.17869 10.1524" width="6.17869pt"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path id="g50-43" d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z"/></g></svg>236 (c.67_88del). mtDNA copy number analysis performed on the patient’s muscle showed mtDNA depletion, as expected in a patient with biallelic pathogenic mutations in POLG. This is the first reported case with POLG p.Gly23Serfs<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.04990005pt" id="M2" height="10.1524pt" version="1.1" viewBox="-0.0498162 -10.1025 6.17869 10.1524" width="6.17869pt"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><use xlink:href="#g50-43"/></g></svg>236, discovered in a patient presenting with features of PEO.

Justin Kurtz

Joseph Americo Fernandes

Mahesh Mansukhani

William C. Copeland

Ali B. Naini

Whole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion

Osteopetrosis is a disorder characterized by high bone density, hepatosplenomegaly, visual and hearing loss, and anemia. Pycnodysostosis presents with short stature, acroosteolysis, and dense bones. We, hereby, present here a family with autosomal dominant osteopetrosis and also children with recessive osteopetrosis and pycnodysostosis. The molecular confirmation was done in 3 cases. Genetic heterogeneity in clinical presentation is discussed here. Further studies will help in identifying epigenetic alterations and population-specific variants and also developing targeted therapies.

Parminder Kaur

Inusha Panigrahi

Harleen Kaur

Thakurvir Singh

Chakshu Chaudhry

Overlapping Phenotypes in Osteopetrosis and Pycnodysostosis in Asian-Indians

LEOPARD syndrome is a rare congenital anomaly that involves several organs. Patients with this syndrome develop multiple lentigines resembling a leopard&#x2019;s hide. LEOPARD is an acronym of the major features constituting the syndrome including lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary valve stenosis, anomalies of genitalia, retardation of growth, and deafness. The syndrome is rare, and only 200 cases have been reported yet worldwide. We present the case of an 8-year-old female patient who visited the Ho Chi Minh City Hospital of Dermato-Venereology because of multiple brownish-black &#x201c;dots&#x201d; on her face and body. On examination, she also showed abnormalities in the maxillofacial bones, vertebrae, shoulders, sternum, and teeth, as well as deaf-mutism and growth retardation, which are typical of LEOPARD syndrome. Genetic analysis revealed a PTPN11 gene mutation in this case. To the best of our knowledge, this is the first case of LEOPARD syndrome reported in Vietnam.

Hao Trong Nguyen

Nguyen Nhat Pham

Hoang Anh Vu

Tu Nguyen Anh Tran

The First Vietnamese Patient of LEOPARD Syndrome due to a PTPN11 Mutation: A Case Report and Review of the Literature

Jamie H. Choi

Rachel Li

Rachel Gannaway

Tahnee N. Causey

Anna Harrison

Natario L. Couser

Corrigendum &#x0023;2 to &#x201c;Eye Manifestations of Shprintzen&#x2013;Goldberg Craniosynostosis Syndrome: A Case Report and Systematic Review&#x201d;

In this clinical report, we describe a male infant and his mother, who had similar congenital heart defects. They were both diagnosed neonatally with total anomalous pulmonary venous connection (TAPVC) in combination with other heart defects. Neither of the two had any other organ malformations or dysmorphic facial features. SNP-array identified a central 22q11.2 microdeletion in the male infant and his mother as well as in the maternal grandmother and maternal aunt. The mother and the maternal aunt additionally harbored a 15q11.2 BP1-BP2 microdeletion. The maternal grandmother was unaffected by heart disease. However, heart computed tomography scan of the maternal aunt revealed a quadricuspid aortic valve. Additionally, the maternal grandmother and the maternal aunt both had significant learning disabilities. Rarely, TAPVC has been described in patients with the common 22q11.2 microdeletions. However, to the best of our knowledge, TAPVC has not previously been reported in patients with this small central 22q11.2 microdeletion. Haploinsufficiency of TBX1 was originally thought to be the main cause of the 22q11.2 microdeletion syndrome phenotype, but TBX1 is not included in the atypical central 22q11.2 microdeletion. Previous reports have suggested an association between TAPVC and the 15q11.2 BP1-BP2 microdeletion. Our report does not support this association as the maternal aunt, who harbors both microdeletions, is unaffected by TAPVC, and the male infant affected by TAPVC does not harbor the 15q11.2 BP1-BP2 microdeletion. Our findings support that genes located in the central 22q11.2 region are important for heart development and that haploinsufficiency of these genes plays a crucial role in the development of the rare heart defect TAPVC.

Signe Faurschou

Dorte L. Lildballe

Lisa L. Maroun

Morten Helvind

Maria Rasmussen

Total Anomalous Pulmonary Venous Connection in Mother and Son with a Central 22q11.2 Microdeletion

Intracranial undifferentiated pleomorphic sarcoma remains a rare pathology within the sarcoma literature that may arise primarily or secondary after radiation therapy. Despite first-line treatment with maximal surgical resection, followed by nonstandardized adjuvant chemotherapy/radiation regimens, clinical prognosis remains exceedingly poor. Furthermore, there is a lack of genetic or molecular characterization to guide potential for targeted therapies. We present genomic analysis of a radiation-induced intracranial undifferentiated pleomorphic sarcoma in an 83-year-old woman with notable KIT and PDGFRA alterations. Further similar genomic studies of intracranial pleomorphic sarcoma are needed to develop better therapies for this rare but challenging disease entity.

Christopher S. Hong

Edwin Partovi

James Clune

Anita Huttner

Henry S. Park

Sacit Bulent Omay

Genomic Characterization of Radiation-Induced Intracranial Undifferentiated Pleomorphic Sarcoma

We report a 15-year-old boy with cat-eye syndrome (CES) without short stature or intellectual disorder. The boy was confirmed by cytogenetic and high-resolution chromosome microarray analysis (CMA). The G-banding karyotype confirmed the de novo of the patient. Also, the CMA result showed 1.76&#x2009;Mb tetrasomy of proximal 22Q11.1&#x2009;&#x27f6;&#x2009;22Q11.21 consistent with CES {arr22q11.1q11.21 (16,888,899&#x2013;18,644,241) X4}, a typical small type I CES chromosome. The patient has many of the basic characteristics of CES; however, he is taller than his peers instead of shorter. It is rarely reported in the past since short stature is a common feature of this syndrome. Furthermore, the boy has no intellectual disorder and attends a normal school since he was six-year-old. What bothered him most were recurrent respiratory infections, retromicrognathia, and heart defects.

Jinjie Li

Yue Zhang

Yanjun Diao

Rui Li

Liqing Jiang

Lei Zhou

Jiayun Liu

Weixun Duan

Liu Yang

A De Novo sSMC (22) Characterized by High-Resolution Chromosome Microarray Analysis in a Chinese Boy with Cat-Eye Syndrome

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Case Reports in Genetics publishes case reports and case series focusing on diseases caused by hereditary predisposition or genetic variation in individuals and families.

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Case Reports in Genetics - Table of contents 2021

title

Case Reports in Genetics publishes case reports and case series focusing on diseases caused by hereditary predisposition or genetic variation in individuals and families.

Case Reports in Genetics