Shahida Moosa

Stellenbosch University | SUN · Division of Molecular Biology and Human Genetics (Medical Genetics)

Osteogenesis imperfecta (OI) comprises a genetically heterogeneous group of skeletal fragility diseases. Here, we report on five independent families with a progressively deforming type of OI, in whom we identified four homozygous truncation or frameshift mutations in MESD. Affected individuals had recurrent fractures and at least one had oligodont...

Many monogenic disorders cause a characteristic facial morphology. Artificial intelligence can support physicians in recognizing these patterns by associating facial phenotypes with the underlying syndrome through training on thousands of patient photographs. However, this ‘supervised’ approach means that diagnoses are only possible if the disorder...

The Undiagnosed Disease Program in South Africa (UDP) sought to prospectively evaluate the clinical utility of exome sequencing (ES) in a phenotypically diverse, multi‐ethnic cohort of South African patients with suspected rare genetic disorders. ES was undertaken in 100 sequential patients (93 singletons, 3 duos, and 4 trios) recruited to the UDP...

Most individuals with rare diseases initially consult their primary care physician. For a subset of rare diseases, efficient diagnostic pathways are available. However, ultra-rare diseases often require both expert clinical knowledge and comprehensive genetic diagnostics, which poses structural challenges for public healthcare systems. To address t...

Aicardi-Goutières syndrome (AGS) refers to a group of genetic diseases characterised by severe inflammatory encephalopathy that usually present within the first year of life, resulting in progressive loss of cognition, spasticity, dystonia and motor disability. Pathogenic variants in the adenosine deaminase acting on RNA ( Adar ) enzyme have been l...

The field of clinical genetics and genomics continues to evolve. In the past few decades, milestones like the initial sequencing of the human genome, dramatic changes in sequencing technologies, and the introduction of artificial intelligence, have upended the field and offered fascinating new insights. Though difficult to predict the precise paths...

Hyperphosphatasia with mental retardation syndrome (HPMRS), also known as Mabry syndrome, is an autosomal recessive disease that is associated with inherited glycosylphosphatidylinositol (GPI) deficiencies. This genetically heterogeneous disorder can be caused by variants in seven genes that encode molecules of the glycosylphosphatidylinositol (GPI...

Objectives The developmental and epileptic encephalopathies (DEE) are a heterogeneous group of rare neurodevelopmental disorders, characterised by early-onset seizures that are often intractable, electroencephalographic abnormalities, and developmental delay or regression. There is a paucity of data from sub-Saharan Africa on the genetic basis of D...

Renal cell carcinoma is rarely described in pediatric patients with tuberous sclerosis complex. This report describes a case of an 11-year old male with tuberous sclerosis-associated renal cell carcinoma.

Short stature is one of the most common reasons for a referral to the pediatric endocrinology clinic. Thousands of patients with short stature are assessed annually at the Department of Endocrine and Metabolic Diseases (DEMD) at Bab el Oued University Hospital in Algiers, Algeria. However, diagnostic rates in patients with syndromic short stature a...

Hemizygous loss-of-function variants in the non-POU domain-containing, octamer-binding gene, NONO, cause X-linked mental retardation syndrome 34 (MRXS34). Here, we describe the 12th patient in the literature with this rare syndrome, the first affected male from sub-Saharan Africa. This South African patient presented with dysmorphic features, conge...

Skeletal ciliopathies are a heterogenous group of disorders with overlapping clinical and radiographic features including bone dysplasia and internal abnormalities. To date, pathogenic variants in at least 30 genes, coding for different structural cilia proteins, are reported to cause skeletal ciliopathies. Here, we summarize genetic and phenotypic...

The majority of monogenic disorders cause craniofacial abnormalities with characteristic facial morphology. These disorders can be diagnosed more quickly by using computer-aided next-generation phenotyping tools, such as DeepGestalt. These tools have learned to associate facial phenotypes with the underlying syndrome through training on thousands o...

The majority of monogenic disorders cause craniofacial abnormalities with characteristic facial morphology. These disorders can be diagnosed more efficiently with the support of computer-aided next-generation phenotyping tools, such as DeepGestalt. These tools have learned to associate facial phenotypes with the underlying syndrome through training...

A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish emb...

Floating-Harbor syndrome (FHS) is a rare autosomal dominant syndrome characterized by short stature with delayed bone age, retarded speech development, intellectual disability and dysmorphic facial features. Recently, dominant mutations almost exclusively clustered in the final exon of the Snf2-related CREBBP activator protein ( SRCAP ) gene were i...

Osteogenesis imperfecta (OI) is the most common skeletal dysplasia, which predisposes to recurrent fractures and bone deformity and presents with wide clinical variability. More than 80% of OI cases are related to dominantly inherited mutations in COL1A1 or COL1A2. The rest of the cases, however, involve many other noncollagen genes, all of which a...

Background Very recently, compound heterozygous loss‐of‐function mutations in TELO2 were shown to underlie the newly‐described You‐Hoover‐Fong syndrome. TELO2 forms part of the co‐chaperone triple T complex (TTT complex), which plays an important role in the maturation and stabilization of the phosphatidylinositol 3‐kinase‐related protein kinases (...

Smith-Lemli-Opitz syndrome (SLOS; OMIM 270400) is a well known autosomal recessively inherited multiple congenital malformation syndrome. Typical limb malformations seen in individuals with SLOS include post-axial polydactyly and 2-3 toe cutaneous syndactyly. We present 2 unrelated 20-week fetuses with striking abnormalities involving the hands and...

Since the original description of the IARS2-related cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, skeletal dysplasia syndrome (CAGSSS; OMIM616007) in an extended consanguineous family of French–Canadian descent, no further patients have been reported. IARS2 (OMIM 612801) encodes the mitochondrial isoleucinetR...

A thanatophoric dysplasia type I case with a FGFR3 p.R248C mutation and survival beyond the neonatal period: Thanatophoric dysplasia, is a severe congenital anomaly which mostly causes stillbirth or death of the affected baby within hours due to respiratory insufficiency. The diagnosis of TD is typically suspected on ultrasound during the second tr...

Heterozygous germline mutations inMTOR have been shown to underlie Smith–Kingsmore syndrome, a rare autosomal dominant syndrome characterized by macrocephaly, developmental delay, and dysmorphic facial features. Recently, two unrelated families with the MTOR mutation, c.5395G>A p.(Glu1799Lys), were reported. Here, we describe siblings from a non-co...

The cover image, by Shahida Moosa et al., is based on the Research Letter A novel homozygous PAM16 mutation in a patient with a milder phenotype and longer survival, DOI: 10.1002/ajmg.a.37823.

Recently, a homozygous founder mutation in PAM16 (MAGMAS; OMIM 614336), p.N76D, was shown to underlie the very rare lethal spondylometaphyseal dysplasia type M�egarban�e–Dagher–Melki type (SMDMDM; OMIM 613320) in four patients from two unrelated consanguineous Lebanese families [Mehawej et al., 2014]. Here, we report on a patient with a novel homoz...

Cranioectodermal dysplasia (CED), also known as Sensenbrenner syndrome, is an autosomal recessive ciliary chondrodysplasia characterized by a recognizable craniofacial gestalt, skeletal abnormalities, and ectodermal features. To date, four genes have been shown to underlie the syndrome, namely, IFT122 (WDR10), WDR35 (IFT121), IFT43 (C14orf179), and...

The fibroblast growth factor (FGF) signalling pathway has been the focus of intense genetic and functional research for several decades. The emerging data implicate FGF signalling in diverse regulatory processes, both in the developing embryo as well as in the adult organism. Alterations in this tightly regulated pathway can lead to a number of pat...

Filippi syndrome is a rare, presumably autosomal-recessive disorder characterized by microcephaly, pre- and postnatal growth failure, syndactyly, and distinctive facial features, including a broad nasal bridge and underdeveloped alae nasi. Some affected individuals have intellectual disability, seizures, undescended testicles in males, and teeth an...

Background: While international studies show thyroid dysfunction occurs more commonly in individuals with Down syndrome (DS) than in the general population, there is a paucity of available data from sub-Saharan Africa. Objectives: To document the range of thyroid function in a cohort of South African children with DS, and to assess referral and...

Pseudoachondroplasia is an autosomal dominant skeletal dysplasia that results in disproportionately short stature, severe brachydactyly with strikingly lax small joints, malalignments of the lower limbs, and characteristic radiological features. Although named ‘false achondroplasia’, the entity is a distinct condition, in which affected individuals...

Osteogenesis imperfecta (OI) is a heterogeneous group of genetic bone disorders that are characterised by decreased bone mass, increased bone fragility and susceptibility to fractures. The severe, perinatal lethal form (Type II) (OMIM 166210) is characterised by bone fragility, with perinatal fractures, severe bowing of long bones, undermineralisat...

Sirenomelia, also known as the 'mermaid malformation/syndrome', is a rare, serious congenital anomaly characterized by variable degrees of fusion of the lower limbs and associated severe malformations of the lower vertebral and genitourinary systems. In this report, we describe a series of African patients with sirenomelia. We present the clinical...

The Division of Human Genetics (National Health Laboratory Service and University of the Witwatersrand) recently hosted the second annual Achondroplasia Day in Johannesburg. Participation in the meeting increased from 4 families in 2011 to 17 families in 2012. The main aim of the meeting was to bring individuals with achondroplasia and their famili...